A novel maturation index based on neonatal diffusion tensor imaging reflects typical perinatal white matter development in humans

Human birth presents an abrupt transition from intrauterine to extrauterine life. Here we introduce a novel Maturation Index (MI) that considers the relative importance of gestational age at birth and postnatal age at scan in a General Linear Model. The MI is then applied to Diffusion Tensor Imaging (DTI) in newborns for characterizing typical white matter development in neonates. DTI was performed cross-sectionally in 47 neonates (gestational age at birth = 39.1 ± 1.6 weeks [GA], postnatal age at scan = 25.5 ± 12.2 days [SA]). Radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA) along 27 white matter fiber tracts were considered. The MI was used to characterize inflection in maturation at the time of birth using GLM estimated rates of change before and after birth. It is proposed that the sign (positive versus negative) of MI reflects the period of greatest maturation rate. Two general patterns emerged from the MI analysis. First, RD and AD (but not FA) had positive MI on average across the whole brain (average MI_AD = 0.31 ± 0.42, average MI_RD = 0.22 ± 0.34). Second, significant regions of negative MI in RD and FA (but not AD) were observed in the inferior corticospinal regions, areas known to myelinate early. Observations using the proposed method are consistent with proposed models of the white matter maturation process in which pre-myelination is described by changes in AD and RD due to oligodendrocyte proliferation while true myelination is characterized by changes in RD and FA due to myelin formation.     

A diffusion tensor imaging study of deep gray and white matter brain maturation differences between patients with spina bifida cystica and healthy controls

The aim of this study was to use diffusion tensor imaging (DTI) to identify differences in the maturation of deep gray matter (GM) and white matter (WM) between patients with spina bifida cystica (SBC) (n = 29) with normal-appearing brains on conventional MRI, and age-matched and sex-matched healthy control participants (n = 33). Changes in DTI metrics were calculated using a log–linear regression model. We observed increasing fractional anisotropy (FA) with age in the occipital, fornix, cingulum and middle cerebellar peduncles and decreasing FA with age in the genu and splenium of the corpus callosum (CC) and caudate nuclei in patients compared to controls. Increasing FA values in some of the WM structures probably represent faulty WM maturation, whereas decreasing FA values in the CC represents changes secondary to the affected WM fibers contributing to the CC. DTI changes in deep GM and WM in the absence of any abnormality on conventional MRI might provide the basis for cognitive decline in these patients.     

Evaluation of changes in magnetic resonance diffusion tensor imaging of the bilateral optic tract in monocular blind rats

Some studies have used diffusion tensor imaging (DTI) to investigate white matter development of the visual pathway in humans and animals after visual deprivation. However, the alterations in the bilateral optic tract after the transection of unilateral optic nerve have not been well explored. In this study, we attempted to investigate the structural integrity of and pathological changes to the bilateral optic tract after transection of the unilateral optic nerve in rats using DTI. Eight healthy male Sprague-Dawley (SD) rats were randomly divided into 2 groups, with 4 in each group. Group A served as a control group. Transection of the unilateral (right) optic nerve was performed in the four rats in group B at seven days after birth to establish the early monocular blind model. Four months after the operation, MnCl₂ was injected into the left eyes of all rats, and MRI examinations were performed 24 h after injection. We detect the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values of the bilateral optic tract in all rats. In a comparison of the ipsilateral optic tract of group B with group A, a significant decrease in FA (P < 0.001) and an increase in RD (P < 0.01) of the left optic tract were found in group B, while no significant difference was found in the right optic tract. In group B, the FA and RD values of the left optic tract were significantly lower (P < 0.01) and significantly higher (P < 0.05), respectively, than those of the right optic tract. Consequently, transection of the right optic nerve can lead to structural integrity damage of and pathological changes to the left optic tract in rats. Some DTI-derived parameters (such as FA and RD) may serve as biomarkers of optic tract degeneration.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

ObjectiveTo assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.MethodOpen lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.ResultsOne hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.ConclusionIn a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.     

Correlation between cognitive function and the association fibers in patients with Alzheimer’s disease using diffusion tensor imaging

White matter (WM) changes, along with well-characterized cortical abnormalities, occur in patients with Alzheimer’s disease (AD). We investigated the integrity of WM tracts within association fibers by the use of fractional anisotropy (FA), and the relationship between FA values and cognitive function in patients with AD. Neuropsychological examination and conventional MRI, as well as diffusion tensor imaging, (DTI) were conducted on 12 patients with mild to moderate AD and 18 cognitively healthy volunteers. DTI was performed to measure FA in the bilateral inferior fronto-occipital fasciculus (IFOF) and the superior longitudinal fasciculus (SLF). Mini-Mental State Examination (MMSE) scores and Montreal Cognitive Assessment (MoCA) values were used to evaluate cognitive function and the Clinical Dementia Rating (CDR) scale was used as a staging tool for dementia severity. FA measures were analyzed and correlated with neuropsychological data. No patient showed any WM tract abnormality on either T1-weighted or T2-weighted MRI. However, the FA values in the bilateral IFOF and SLF and the MoCA scores in patients with AD were significantly decreased (p < 0.05) compared to the controls. Furthermore, the decreased FA values in the SLF were positively correlated with cognitive function (MMSE scores – right: r = 0.672, p = 0.033, left: r = 0.919, p < 0.01; MoCA values – right: r = 0.747, p = 0.013, left: r = 0.679, p = 0.031). Our findings confirmed that the loss of integrity of microstructural WM connectivity has a role in the cognitive decline of patients with AD. The data also suggest that the FA values of the SLF may be used as a clinical marker of cognitive function.     

White matter microstructural abnormalities in amnestic mild cognitive impairment: A meta-analysis of whole-brain and ROI-based studies

Studies that examined white matter (WM) alterations in amnestic mild cognitive impairment (aMCI) abound. This timely meta-analysis aims to synthesize the results of these studies. Seventy-seven studies (total N_aMCI = 1844) were included. Fourteen region-of-interest-based (ROI-based) (k ≥ 8; N_aMCI ≥ 284 per ROI) and two activation likelihood estimation (ALE) meta-analyses (fractional anisotropy [FA]: k = 15; N_aMCI = 463; mean diffusivity [MD]: k = 8; N_aMCI = 193) were carried out. Among the many significant ROI-related findings, reliable FA and MD alterations in the fornix, uncinate fasciculus, and parahippocampal cingulum were observed in aMCI. Larger effects were observed in MD relative to FA. The ALE meta-analysis revealed a significant FA decrease among aMCI subjects in the posterior corona radiata. These results provide robust evidence of the presence of WM abnormalities in aMCI. Our findings also highlight the importance of carrying out both ROI-based and whole-brain-based research to obtain a complete picture of WM microstructural alterations associated with the condition..     

Influence of white matter anisotropic conductivity on EEG source localization: Comparison to fMRI in human primary visual cortex

ObjectiveThe goal of this study was to experimentally investigate the influence of the anisotropy of white matter (WM) conductivity on EEG source localization.MethodsVisual evoked potentials (VEP) and fMRI data were recorded from three human subjects presented with identical visual stimuli. A finite element method was used to solve the EEG forward problems based on both anisotropic and isotropic head models, and single-dipole source localization was subsequently performed to localize the source underlying the N75 VEP component.ResultsThe averaged distances of the localized N75 dipole locations in V1 between the isotropic and anisotropic head models ranged from 0 to 6.22 ± 2.83 mm. The distances between the localized dipole positions and the centers of the fMRI V1 activations were slightly smaller when using an anisotropic model (7.49 ± 1.35–15.70 ± 8.60 mm) than when using an isotropic model (7.65 ± 1.30–15.31 ± 9.18 mm).ConclusionsAnisotropic models incorporating realistic WM anisotropic conductivity distributions do not substantially improve the accuracy of EEG dipole localization in the primary visual cortex using experimental data obtained using visual stimulation.SignificanceThe present study represents the first attempt using a human experimental approach to assess the effects of WM anisotropy on EEG source analysis.     

Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders: A randomised controlled study

AimThis study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory.MethodsIn total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (sub-study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ⩽ 14) (sub-study 2). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000 IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were measured at week 1 (baseline) and weeks 5, 9 and 14. HDRS-17 and neuropsychological function was assessed at weeks 1, 9 and 14 using a test battery including the RAVLT Auditory Verbal Learning Test (primary depression and primary cognition outcomes in the original trial).ResultsEPO had no cumulative effect on plasma levels of IL-6 or IL-18 but increased hsCRP levels in patients with TRD (mean ± SD change in ng/L: EPO: 0.43 ± 1.64; Saline: −0.90 ± 2.43; F(1,39) = 4.78, p = 0.04). EPO had no effects on inflammatory markers in BD. There was no correlation between change in inflammatory markers and change in verbal memory.ConclusionsRepeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory pathway is not a putative mechanism of the EPO-associated improvement of cognition in affective disorders.     

Verbal fluency as a possible predictor for psychosis

BackgroundNeurocognitive abnormalities are prevalent in both first episode schizophrenia patients and in ultra high risk (UHR) patients.AimTo compare verbal fluency performance at baseline in UHR in patients that did and did not make the transition to psychosis.MethodBaseline verbal fluency performance in UHR-patients (n = 47) was compared to match first episode patients (n = 69) and normal controls (n = 42).ResultsVerbal fluency (semantic category) scores in UHR-patients did not differ significantly from the score in first episode schizophrenia patients. Both the UHR group (p < 0.003) and the patient group (p < 0.0001) performed significantly worse than controls. Compared to the non-transition group, the transition group performed worse on verbal fluency, semantic category (p < 0.006) at baseline.ConclusionsVerbal fluency (semantic category) is disturbed in UHR-patients that make the transition to psychosis and could contribute to an improved prediction of transition to psychosis in UHR-patients.     

Impacto de la estimulación subtalámica a largo plazo sobre la situación cognitiva de los pacientes con enfermedad de Parkinson avanzada

ObjectiveThe aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery.Material and methodsWe conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2 ± 8.2 years; mean progression time of 14.1 ± 6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini–Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS).ResultsPatients were found to score lower on the MMSE (−0.89%), clock-drawing test (−2.61%), MDRS (−1.72%), and especially phonemic (−13.28%) and sematic verbal fluency tests (−12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (−10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (−16.87%), WAIS-III-LN (−16.67%), and JLO test (−11.56%).DiscussionIn our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD.     

Evaluation of cognitive function in bipolar disorder using the Brief Assessment of Cognition in Affective Disorders (BAC-A)

BackgroundAlthough cognitive impairment is a core feature of bipolar disorder (BD) there is no instrument of choice for the assessment of bipolar patients. The aim of this study is to assess cognitive performance using the Brief Assessment of Cognition in Affective Disorders (BAC-A), a comprehensive test battery developed specifically for BD, and determine its suitability to estimate global functioning.MethodsThe BAC-A was administered to 93 BD patients (M ± S.E: 35.18 ± 1.39 years) and 56 healthy controls (HC – M ± S.E: 36.17 ± 1.91 years). The scores of the BAC-A were combined in eight summary scores: visuomotor, immediate affective and non-affective memory, verbal fluency, delayed affective and non-affective memory, inhibition, and problem solving. Post hoc analyses were performed on subtests of the summary scores found to be significantly different between BD patients and HC. Correlational analyses explored the association between the Global Assessment of Functioning (GAF) score and cognitive functioning.ResultsCompared to HC, BD patients showed a significant impairment in short-term non-affective memory and verbal fluency. Poorer performance in verbal memory and verbal fluency summary scores correlated positively with reduced GAF.ConclusionsOur results are consistent with previous reports of verbal memory and verbal fluency impairment in BD. The deficits in short-term memory and semantic fluency may indicate inefficient learning strategies and/or difficulties in retrieving information. The BAC-A could be used to estimate global functioning in BD patients.     

Lifetime presence of psychotic symptoms in bipolar disorder is associated with less favorable socio-demographic and certain clinical features

BackgroundThe presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the “with psychotic features” specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area.MethodsThe present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N = 360), with (BDPs, N = 207) and without a lifetime history of psychosis (BDNPs, N = 153).ResultsAn overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7 ± 10.5 vs 30.1 ± 12.3 years; p = 0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p < 0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p < 0.001) and most recent episode (69.8% vs 35.6%; p < 0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p = 0.002), more lifetime hospitalizations (3.8 ± 6.1 vs 2 ± 3; p = 0.002) and involuntary commitments (1 ± 1.9 vs 0.1 ± 0.4; p < 0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p = 0.001), more current antipsychotic use (90.1% vs 70.9%; p < 0.001), and lower GAF (62.3 ± 14.2 vs 69.3 ± 12.5; p < 0.001), but shorter duration of most recent episode (34.1 ± 45.4 vs 50.3 ± 65.7 days; p = 0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p = 0.005), and antidepressant use (19.4% vs 56.6%; p < 0.001).ConclusionsThe present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.     

Cerebellar involvement in essential tremor with and without resting tremor: A Diffusion Tensor Imaging study

ObjectiveEssential Tremor with resting tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI).MethodsWe studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres.ResultsMD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). Interestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM.ConclusionOur results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.     

Behavioral inhibition in children with learning disabilities

Children with reading disabilities (RD, n = 17), mathematical disabilities (MD, n = 22), combined reading and mathematical disabilities (RD + MD, n = 28) and control peers (n = 45) were tested on behavioral inhibition with a Go/no-go task in a picture, letter and digit-modality. In contrast to children without RD, children with RD made significantly more commission errors on alphanumeric (letter and digit) modalities compared to the non-alphanumeric picture modality. As compared to children without MD, children with MD made as much commission errors on the picture modality as on the letter modality. No significant interaction-effect was found between RD and MD. These results can be considered as evidence for behavioral inhibition deficits related to alphanumeric stimuli in children with RD but not in children with MD.     

Evaluation of frequency-selective non-linear blending technique on brain CT in postoperative children with Moyamoya disease

ObjectiveTo evaluate whether a frequency-selective non-linear blending (BC) technique can improve tissue contrast and infarct detection on non-enhanced brain CT (NECT) in postoperative Moyamoya (MMD) patients.Materials and methodsFrom January 2010 to December 2017, 33 children (13 boys and 20 girls; mean age 9.1 ± 3.4 years) with MMD postoperatively underwent NECT followed by diffusion MRI. We compared the contrast-to-noise ratio (CNR) between gray matter (GM) and white matter (WM) in NECT and BC images and the CNR between the infarct lesion and adjacent normal-appearing brain in NECT and BC images using a paired t-test. We assessed image noise, GM-WM differentiation, artifacts, and overall quality using a Wilcoxon signed rank test. A McNemar two-tailed test was conducted to compare the diagnostic accuracy of infarct detection.ResultsThe CNR between GM and WM and the CNR of the infarct was better in BC images than in NECT images (3.9 ± 1.0 vs. 1.8 ± 0.6, P < 0.001 and 3.6 ± 0.3 vs. 1.9 ± 0.2, P < 0.001), with no difference in overall image quality observed. The sensitivity and specificity of infarct detection were 55.0% and 76.9% using NECT, and 70.0% and 69.2% using BC technique. The diagnostic accuracy of NECT and BC technique was 63.6% (21/33) and 69.7% (23/33), respectively.ConclusionThis study showed that the BC technique improved CNR and maintained image quality. This technique may also be used to identify ischemic brain changes in postoperative MMD patients by improving the CNR of the infarct lesion.     

The role of set-shifting in auditory verbal hallucinations

BackgroundAuditory verbal hallucinations (AVHs) are a cardinal characteristic of psychosis. Recent research on the neuropsychological mechanism of AVHs has focused on source monitoring failure, but a few studies have suggested the involvement of attention, working memory, processing speed, verbal learning, memory, and executive functions. In this study we examined the neuropsychological profile of patients with AVHs, assuming that the mechanism underlying this symptom could be a dysfunction of specific cognitive domains.MethodsA large neuropsychological battery including set-shifting, working memory, processing speed, attention, fluency, verbal learning and memory, and executive functions was administered to 90 patients with psychotic disorders and 44 healthy controls. The group of patients was divided into two groups: 46 patients with AVHs in the current episode and 44 who denied auditory hallucinations or other modalities in the current episode. AVHs were assessed with the Psychotic Symptom Rating Scales (PSYRATS); the Launay-Slade Hallucination Scale was used to measure long-term propensity to auditory verbal hallucination-like experiences (HLEs) in the sample.ResultsPatients showed poorer performances on all neuropsychological measures compared to the healthy controls' group. In the original dataset without missing data (n = 58), patients with AVHs (n = 29) presented poorer set shifting and verbal learning, higher levels of visual attention, and marginally significant poorer semantic fluency compared to patients without AVHs (n = 29). In the logistic model on the multiple imputed dataset (n = 90, 100 imputed datasets), lower capacity of set shifting and semantic fluency distinguished patients with AVHs from those without them.ConclusionsPatients experiencing persistent AVHs might fail to shift their attention away from the voices; poorer semantic fluency could be a secondary deficit of set-shifting failure.     

Diffusion tractography of the fornix in schizophrenia

BackgroundWhite matter fiber tracts, especially those interconnecting the frontal and temporal lobes, are likely implicated in pathophysiology of schizophrenia. Very few studies, however, have focused on the fornix, a compact bundle of white matter fibers, projecting from the hippocampus to the septum, anterior nucleus of the thalamus and the mamillary bodies. Diffusion Tensor Imaging (DTI), and a new post-processing method, fiber tractography, provides a unique opportunity to visualize and to quantify entire trajectories of fiber bundles, such as the fornix, in vivo. We applied these techniques to quantify fornix diffusion anisotropy in schizophrenia.MethodsDTI images were used to evaluate the left and the right fornix in 36 male patients diagnosed with chronic schizophrenia and 35 male healthy individuals, group matched on age, parental socioeconomic status, and handedness. Regions of interest were drawn manually, blind to group membership, to guide tractography, and fractional anisotropy (FA), a measure of fiber integrity, was calculated and averaged over the entire tract for each subject. The Doors and People test (DPT) was used to evaluate visual and verbal memory, combined recall and combined recognition.ResultsAnalysis of variance was performed and findings demonstrated a difference between patients with schizophrenia and controls for fornix FA (p = 0.006). Protected post-hoc independent sample t-tests demonstrated a bilateral FA decrease in schizophrenia, compared with control subjects (left side: p = 0.048; right side p = 0.006). Higher fornix FA was statistically significantly correlated with DPT and measures of combined visual memory (r = 0.554, p = 0.026), combined verbal memory (r = 0.647, p = 0.007), combined recall (r = 0.516, p = 0.041), and combined recognition (r = 0.710, p = 0.002) for the control group. No such statistically significant correlations were found in the patient group.ConclusionsOur findings show the utility of applying DTI and tractography to study white matter fiber tracts in vivo in schizophrenia. Specifically, we observed a bilateral disruption in fornix integrity in schizophrenia, thus broadening our understanding of the pathophysiology of this disease.     

The role of white matter in personality traits and affective processing in bipolar disorder

BackgroundBipolar disorder (BD) is characterized by affective processing bias and variations in personality traits. It is still unknown whether these features are linked to the same structural brain alterations. The aim of this study was to investigate relationships between specific personality traits, white matter (WM) properties, and affective processing in BD and HC.Methods24 healthy controls (HC) and 38 adults with BDI (HC: 29.47 ± 2.23 years, 15 females; BDI: 32.44 ± 1.84 years, 20 females) completed clinical scales and the Big Five Inventory. They were also administered the Affective Go/No-Go (AGN) and the Rapid Visual Processing (RVP) tasks of the Cambridge Neuropsychological Test Automated Battery. Diffusion Tensor Imaging (DTI) assessed the microstructure of WM tracts.ResultsIn BDI measures of WM properties were reduced across all major brain white matter tracts. As expected, individuals with BDI reported greater neuroticism, lower agreeableness and conscientiousness, and made a greater number of errors in response to affective stimuli in the AGN task compared to HC. High neuroticism scores were associated with faster AGN latency, and overall reduced AGN accuracy in both HC and BDI. Elevated FA values were associated with reduced neuroticism and increased cognitive processing in HC but not in BDI.ConclusionsOur findings showed important potential links between personality, affective processing and WM integrity in BD. In the future therapeutic interventions for BD using brain stimulation protocols might benefit from the use of DTI to target pathways underlying abnormal affective processing.     

Interictal serum brain-derived neurotrophic factor level reflects white matter integrity,epilepsy severity,and cognitive dysfunction in chronic temporal lobe epilepsy

ObjectiveMost patients with temporal lobe epilepsy (TLE) have epileptic foci originating from the medial temporal lobe, particularly the hippocampus. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor mainly expressed in the hippocampus, though it is not known whether the circulating level of BDNF reflects cognitive performance or white matter structural changes in chronic TLE.MethodsThirty-four patients with TLE and 22 healthy controls were enrolled for standardized cognitive tests, diffusion tensor imaging, and serum BDNF measurement. The patients were further divided into a subgroup with unilateral TLE (n = 23) and a subgroup with bilateral TLE (n = 11) for clinical and neuroimaging comparisons.ResultsThere were significantly lower BDNF levels in the patients with TLE compared with the controls, with significance contributed mainly from the subgroup with bilateral TLE, which also had more frequent seizures. The BDNF levels correlated with epilepsy duration (σ = − 0.355; p = 0.040) and fractional anisotropy (FA) in the left temporal lobe, left thalamus, and right hippocampus. Using a regression model, BDNF level predicted verbal memory score. Further, design fluency scores were predicted by serum BDNF level via the interactions with left temporal FA.ConclusionsSerum BDNF levels reflected longer epilepsy duration, impaired white matter integrity, and poor cognitive function in patients with chronic TLE.     

White matter disruption is associated with persistent seizures in tuberous sclerosis complex

Background and aimsWhite matter is diffusely altered in tuberous sclerosis complex (TSC), and these alterations appear to be more evident in subjects with a more severe neurologic phenotype. However, little is known on the correlation between white matter alterations and epilepsy in TSC. The aims of this study were to evaluate the effects of early onset and refractory seizures on white matter by using diffusion tensor imaging (DTI).MethodsWe enrolled 20 children with TSC and epilepsy onset in the first 3 years of life and grouped them according to seizure persistence or freedom. All patients underwent brain MRI with DTI. Specific ROIs have were placed to generate tracks to calculate fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Statistical analysis was performed by ANOVA.ResultsChildren with persistent seizures presented an overall reduced FA, with statistically significant differences on the cingulum (right p = 0.003, left p = 0.016), the left cerebral peduncle (p = 0.020), the superior cerebellar peduncles (right p = 0.008, left p = 0.002), the posterior limbs of internal capsule (right p = 0.037, left p = 0.015), the external capsule (right p = 0.018, left p = 0.031), the inferior frontooccipital fasciculus (right p = 0.010, left p = 0.026), and the temporal trunk (right p = 0.017, left p = 0.001).ConclusionsOur study demonstrated that children with persistent seizures present more significant alterations of brain connectivity in areas crucial for global cognitive maturation, executive functions, and verbal abilities, implying a higher risk of cognitive impairment, attention-deficit hyperactivity disorder, and autism.