Impaired interhemispheric connectivity in medication-naive patients with major depressive disorder

Background

Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in major depressive disorder (MDD). The purpose of this study was to investigate interhemispheric connectivity in medication-naive patients with MDD by measuring fractional anisotropy in the CC with diffusion tensor imaging (DTI) techniques.

Methods

We obtained DTI scans from medication-naive patients with MDD and from matched healthy controls. Fractional anisotropy values were compared using semiautomatic region of interest methods to localize the regional CC differences between these 2 groups.

Results

We enrolled 27 patients and 27 controls in our study. Fractional anisotropy values were significantly lower in the anterior genu of the CC in the MDD group than in the control group (p = 0.009, corrected); results were not significantly different in any other CC subregions.

Limitations

As patients with MDD were already experiencing acute episodes, future studies of individuals at risk for MDD are warranted to elucidate the interhemispheric connectivity abnormalities associated with the predisposition to MDD.

Conclusion

The findings demonstrate abnormalities in the structural integrity of the anterior genu of the CC in medication-naive individuals with MDD, which may contribute to impairment of interhemispheric connectivity in patients with this disorder.     

White matter microstructure in patients with obsessive-compulsive disorder

Background

Previous diffusion tensor imaging (DTI) studies in patients with obsessive–compulsive disorder (OCD) have reported inconsistent findings, and it is not known whether observed findings are related to abnormalities in axonal structure or myelination.

Methods

In this DTI study, we investigated fractional anisotropy, as well as axial and radial diffusivity, in 21 patients with OCD and 29 healthy controls.

Results

We found decreased fractional anisotropy in the body of the corpus callosum in the OCD group, which was underpinned by increased radial diffusivity.

Limitations

The cross-sectional design was the main limitation.

Conclusion

Our findings of increased radial diffusivity provide preliminary evidence for abnormal myelination in patients with OCD.     

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Background

Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear.

Methods

We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI).

Results

We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls.

Limitations

The major limitation of our study is the small number of patients with bipolar disorder.

Conclusion

Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.     

Alterations in White Matter Evident Before the Onset of Psychosis

Background

Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.

Methods

Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.

Results

At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to controls, first-episode patients showed widespread reductions in FA and increases in diffusivity. DTI indices in the UHR group were intermediate relative to those in the other 2 groups. Longitudinal analysis revealed a significant group by time interaction in the left frontal WM (P < .001). In this region, there was a progressive reduction in FA in UHR subjects who developed psychosis that was not evident in UHR subjects who did not make a transition.

Conclusions

People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia. The onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.     

Associated factors of quality of life in first-episode schizophrenia patients

Objective

Improving quality of life is an important goal in the treatment of schizophrenia. In previous research, quality of life has been reported to be compromised in patients with schizophrenia. The aim of this study was to investigate whether quality of life may be impaired in first-episode schizophrenia patients and to identify the associated factors of quality of life in first-episode schizophrenia.

Methods

Forty-eight patients with first-episode schizophrenia and 20 normal controls were recruited. Quality of life was measured by using the Quality of Life scale (QLS). General and social self-efficacy, perceived social support were measured by using the self-report scales. The clinical assessments and comprehensive neurocognitive battery were also administered.

Results

First-episode group showed significantly decreased QLS total and QLS subscale scores compared to normal controls group. The key associated factors of quality of life in patients with first-episode schizophrenia were the negative symptoms and social self-efficacy.

Conclusion

This finding implies that compromised quality of life may be already emerged in schizophrenia in their first-episode and the psychosocial interventions should be targeting the negative symptoms and the psychosocial protective factors including self-efficacy in addition to simply ameliorating the positive symptoms to foster social reintegration and recovery of first-episode patients.     

Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

Background

Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.

Methods

We obtained high-resolution 3-dimensional T₁-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse.

Results

We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psycho-pathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.

Limitations

This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.

Conclusion

Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.     

Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD

Background

Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI.

Method

A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms “DTI” or “diffusion tensor;” “whole brain” or “voxel-based;” and “depress^*.” Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region.

Results

We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum.

Limitations

The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences.

Conclusion

Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This is strong evidence for the involvement of these neural circuits in the pathology of MDD.     

Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive-compulsive disorder

Background

There is evidence to suggest that obsessive–compulsive disorder (OCD) is associated with structural abnormalities in cortico–striato–thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD.

Methods

Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callosum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD.

Results

There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores.

Limitations

Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive–compulsive symptom profiles; we did not distinguish between different obsessive–compulsive symptom dimensions.

Conclusion

The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a corticostriatal model of OCD.     

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Background

Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR.

Methods

We recruited 29 UHR patients, 23 first-episode patients and 29 age-and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail.

Results

Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR.

Limitations

Our study had a small sample size, and we were unable to control for the effects of medication.

Conclusion

Our findings suggest that parts of the hippocampal–amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizophrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.     

Emotion-elicited gamma synchrony in patients with first-episode schizophrenia: a neural correlate of social cognition outcomes

Background

Schizophrenia may be understood as a disorder of neural synchrony. There is also increasing evidence that emotional and social cognitive impairments are central to this disorder. In patients with first-episode schizophrenia, we examined whether emotion perception is associated with disruptions to high-frequency (40 Hz) gamma synchrony and whether these disruptions predict self-regulatory adaptive compensations reflected in social cognitive behaviours.

Methods

We obtained electroencephalography recordings from 28 patients with first-episode schizophrenia and matched healthy controls during perception of facial emotion under both conscious and nonconscious conditions. We extracted gamma-band synchrony from the electroencephalogram. We also used behavioural measures of emotion identification, emotional intelligence, negativity bias and social function, along with ratings of first-episode schizophrenia symptoms. We analyzed group differences and predicted social cognition to assess the potential contribution of medication.

Results

Within 200 ms poststimulus, patients with first-episode schizophrenia showed alterations in gamma synchrony during both conscious and nonconscious emotion perception. Stimulus-locked synchrony was reduced in patients, particularly over the temporal cortex, whereas complementary enhancements in absolute gamma synchrony (independent of stimuli) were more distributed over temporal and left parieto-occipital regions. This pattern of altered synchrony predicted poor performance on each measure of social cognition among these patients. Medication dosage did not correlate significantly with either gamma synchrony or behavioural measures in this group.

Limitations

Limitations to our study include the lack of comparison between medicated and unmedicated patients or between types of medication.

Conclusion

These findings suggest that disruptions in integrative processing of motivationally important stimuli show promise as a potential biological marker of social cognitive impairments, present from the first episode of schizophrenia, and their outcomes.     

Evidence for white matter disruption in traumatic brain injury without macroscopic lesions

Background

Non‐missile traumatic brain injury (nmTBI) without macroscopically detectable lesions often results in cognitive impairments that negatively affect daily life.

Aim

To identify abnormal white matter projections in patients with nmTBI with cognitive impairments using diffusion tensor magnetic resonance imaging (DTI).

Methods

DTI scans of healthy controls were compared with those of 23 patients with nmTBI who manifested cognitive impairments but no obvious neuroradiological lesions. DTI was comprised of fractional anisotropy analysis, which included voxel‐based analysis and confirmatory study using regions of interest (ROI) techniques, and magnetic resonance tractography of the corpus callosum and fornix.

Results

A decline in fractional anisotropy around the genu, stem and splenium of the corpus callosum was shown by voxel‐based analysis. Fractional anisotropy values of the genu (0.47), stem (0.48), and splenium of the corpus callosum (0.52), and the column of the fornix (0.51) were lower in patients with nmTBI than in healthy controls (0.58, 0.61, 0.62 and 0.61, respectively) according to the confirmatory study of ROIs. The white matter architecture in the corpus callosum and fornix of patients with nmTBI were seen to be coarser than in the controls in the individual magnetic resonance tractography.

Conclusions

Disruption of the corpus callosum and fornix in patients with nmTBI without macroscopically detectable lesions is shown. DTI is sensitive enough to detect abnormal neural fibres related to cognitive dysfunction after nmTBI.Cognitive and vocational sequelae are common complications after non‐missile traumatic brain injury (nmTBI) without obvious neuroradiological lesions.^1,2 They may present as memory disturbance, impairments in multitask execution and loss of self‐awareness.³ These symptoms have been attributed to diffuse brain injury and the diffuse loss of white matter or neural networks in the brain.^4,5,6 Currently no accurate method is available for diagnosing and assessing the distribution and severity of diffuse axonal injury. As computed tomography and magnetic resonance imaging (MRI) findings underestimate the extent of diffuse axonal injury and correlate poorly with the final neuropsychological outcome,^7,8 this dysfunction tends to be clinically underdiagnosed or overlooked. Indirect evidence for loss of functional connectivity after nmTBI has been provided by both morphometric and functional neuroimaging studies. Morphometric analysis of nmTBI has shown the relationship between atrophy of the corpus callosum and fornix and the neuropsychological outcome.⁹ Most functional neuroimaging studies conducted after nmTBI have shown that cognitive and behavioural disorders are correlated, with some degree of secondary hypometabolism or hypoperfusion in regions of the cortex.⁵ To date, however, there has been no direct in vivo demonstration of structural disconnections without macroscopically detectable lesions in patients with nmTBI.Diffusion tensor magnetic resonance imaging (DTI), which measures diffusion anisotropy in vivo, is a promising method for the non‐invasive detection of the degree of fibre damage in various disease processes affecting the white matter.^10,11 In biological systems, the diffusional motion of water is impeded by tissue structures, such as cell membranes, myelin sheaths, intracellular microtubules and associated proteins. Motion parallel to axons or myelin sheaths is inhibited to a lesser degree than perpendicular motion, a phenomenon known as diffusion anisotropy.¹² Fractional anisotropy was applied to evaluation of post‐traumatic diffuse axonal injury¹³ and its clinical usefulness described. In a previous study,¹⁴ fractional anisotropy score in the acute stage as an index of injury to white matter showed promise in predicting outcome in patients with traumatic brain injury, by using the regions of interest (ROIs) techniques. MRI voxel‐based analysis, a statistical normalising method, has been developed to reduce interindividual variability and to evaluate the whole brain objectively.^15,16,17 We investigated the regions in the whole brain that are commonly injured in patients having nmTBI with cognitive impairments but no macroscopic lesions, using voxel‐based analysis of fractional anisotropy, referred to as diffusion anisotropy. The advent of DTI has allowed inter‐regional fibre tracking, called magnetic resonance tractography, which reconstructs the three‐dimensional trajectories of white matter tracts.^11,18,19 We also investigated whether magnetic resonance tractography sensitively recognises degeneration of the corpus callosum and fornix in individual patients with nmTBI.     

Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia

Background

Prepulse inhibition (PPI) of the startle reflex is modulated by a complex neural network. Prepulse inhibition impairments are found at all stages of schizophrenia. Previous magnetic resonance imaging (MRI) studies suggest that brain correlates of PPI differ between patients with schizophrenia and healthy controls; however, these studies included only patients with chronic illness and medicated patients. Our aim was to examine the structural brain correlates of PPI in antipsychotic-naive patients with first-episode schizophrenia.

Methods

We performed acoustic PPI assessment and structural MRI (1.5 and 3 T) in men with first-episode schizophrenia and age-matched controls. Voxel-based morphometry was used to investigate the association between PPI and grey matter volumes.

Results

We included 27 patients and 38 controls in the study. Patients had lower PPI than controls. The brain areas in which PPI and grey matter volume correlated did not differ between the groups. Independent of group, PPI was significantly and positively associated with regional grey matter volume in the right superior parietal cortex. Prepulse inhibition and grey matter volume associations were also observed in the left rostral dorsal premotor cortex, the right presupplementary motor area and the anterior medial superior frontal gyrus bilaterally. Follow-up analyses suggested that the rostral dorsal premotor cortex and presupplementary motor area correlations were driven predominantly by the controls.

Limitations

We used 2 different MRI scanners, which might have limited our ability to find subcortical associations since interscanner consistency is low for subcortical regions.

Conclusion

The superior parietal cortex seems to be involved in the regulation of PPI in controls and antipsychotic-naive men with first-episode schizophrenia. Our observation that PPI deficits in schizophrenia may be related to the rostral dorsal premotor cortex and presupplementary motor area, brain areas involved in maintaining relevant sensory information and voluntary inhibition, warrants further study.     

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study

Background

Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions.

Objective

To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age‐related white matter hyperintensities (WMH).

Methods

In the Leukoaraiosis and Disability Study, 567 subjects with age‐related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors.

Results

Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion.

Conclusions

Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal‐lobe‐mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.Corpus callosum is the largest commissural structure consisting of white matter tracts that connect the cerebral hemispheres according to an anterior–posterior topographical organisation. Recent research using diffusion tensor magnetic resonance imaging (MRI) has augmented earlier postmortem findings of corpus callosum topography and has shown that the anterior parts of corpus callosum (rostrum and genu) connect the orbitofrontal, lateral and medial frontal cortices, whereas the body and splenium connect parietal, temporal and occipital homotopic regions.¹ In neurodegenerative diseases, the corpus callosum area is markedly reduced, indicating marked axonal loss.^2,3,4,5 In Alzheimer''s disease, the severity and pattern of corpus callosum atrophy have been associated with cortical neuronal loss⁶ independently of white matter hyperintensities (WMH).⁷ In vascular dementia and other ischaemic conditions, however, corpus callosum atrophy is correlated with WMH and hence may result from subcortical ischaemic damage.^8,9Earlier studies have shown that corpus callosum atrophy is associated with global cognitive status,^5,6,10 but, to date, few studies have investigated the role of regional corpus callosum atrophy in specific cognitive processes. Based on the topographical organisation of corpus callosum, the integrity of its subregions may reflect distinct cognitive deficits. In particular, anterior corpus callosum atrophy may be related to the frontal‐lobe‐mediated executive deficits. Previous work of the Leukoaraiosis and Disability (LADIS) Study has shown that age‐related WMH are associated with cognitive impairment in elderly subjects without dementia.¹¹ Moreover, in these subjects, the corpus callosum area has been found to be inversely related to motor deficits and global cognitive decline.¹² This study examined the independent contribution of regional corpus callosum atrophy to deficits in mental speed, attention and executive functions in a large sample of elderly subjects with WMH by using quantitative MRI analysis and targeted neuropsychological test methods. The demographic and medical background variables, and coexisting WMH were controlled by using multivariate analysis.     

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis

Background

Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance.

Methods

We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-back working memory tasks as well as oddball detection and passive fixation tasks.

Results

We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory–related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls.

Limitations

Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out.

Conclusion

The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.     

Thinning of the Corpus Callosum and Cerebellar Atrophy is Correlated with Phenotypic Severity in a Family with Spastic Paraplegia Type 11

Background

Mutations in the spatacsin gene are associated with spastic paraplegia type 11 (SPG11), which is the most-common cause of autosomal recessive hereditary spastic paraplegia. Although SPG11 has diverse phenotypes, thinning of the corpus callosum is an important feature.

Case Report

Clinical, genetic, and radiological evaluations were undertaken in a large family from Gujarat in North India with hereditary spastic paraplegia, whose affected members presented with varying degrees of spasticity, ataxia, and cognitive impairment. The clinical severity and the degree of corpus callosum and cerebellar atrophy varied among the four affected individuals in the family. Genetic testing of the affected members revealed recessive mutations in the spatacsin gene, consistent with a diagnosis of SPG11.

Conclusions

We believe that the extent of corpus callosum thinning and cerebellar atrophy is correlated with disease severity in affected patients. The addition of extrapyramidal features in the most-affected members suggests that SPG11 exhibits considerable phenotypic heterogeneity.     

Functional and magnetic resonance imaging correlates of corpus callosum in normal pressure hydrocephalus before and after shunting

Background

Normal pressure hydrocephalus (NPH) is associated with corpus callosum abnormalities.

Objectives

To study the clinical and neuropsychological effect of callosal thinning in 18 patients with idiopathic NPH and to investigate the postsurgical callosal changes in 14 patients.

Methods

Global corpus callosum size and seven callosal subdivisions were measured. Neuropsychological assessment included an extensive battery assessing memory, psychomotor speed, visuospatial and frontal lobe functioning.

Results

After surgery, patients showed improvements in memory, visuospatial and frontal lobe functions, and psychomotor speed. Two frontal corpus callosum areas, the genu and the rostral body, were the regions most related to the clinical and neuropsychological dysfunction. After surgery, total corpus callosum and four of the seven subdivisions presented a significant increase in size, which was related to poorer neuropsychological and clinical outcome.

Conclusion

The postsurgical corpus callosum increase might be the result of decompression, re‐expansion and increase of interstitial fluid, although it may also be caused by differences in shape due to cerebral reorganisation.Ventricular dilatation and corpus callosum abnormalities are the anatomical changes most often reported in association with normal pressure hydrocephalus (NPH). Callosal abnormalities include changes in the morphology and the magnetic resonance imaging (MRI) signal. The most consistent findings are stretching, uniform and focal thinning, and upward elevation.^1,2,3,4 Callosal damage has been primarily attributed to lateral ventricle dilatation¹ and to the impingement of the corpus callosum against the falx.²Two studies indicated a partial or complete recovery of different callosal parameters after shunt surgery.^4,5 However, in these studies, only five and eight patients with different types of hydrocephalus were analysed postsurgically. Other studies have reported corpus callosum abnormalities after surgery in 3–17% of cases, including signal changes,^6,7,8,9,10 a transient scalloping deformity⁶ and increased thickness.^7,8 Although the nature of the postsurgical changes in the corpus callosum remains unclear, several causes have been suggested, including callosal compression against the falx, decompression and overdrainage.^6,7,8,9To our knowledge, no morphological MRI quantitative studies of corpus callosum in NPH have been performed to date, nor has the possible involvement of the corpus callosum in the neuropsychological deterioration in NPH been investigated in depth. As damage to the corpus callosum can affect cognition,¹¹ the aim of this study was to investigate the contribution of corpus callosum thinning to the neuropsychological deficits in NPH and to determine the postsurgical callosal changes and their relationship with cognitive outcome.     

Tract-based spatial statistics of diffusion tensor imaging after corpus callosotomy in relation to seizure recurrence

Purpose

To delineate microstructural changes in transected white matter tracts after corpus callosotomy in relation to seizure recurrence using tract-based spatial statistics of diffusion tensor imaging (DTI-TBSS).

Methods

We retrospectively included 12 total corpus callosotomy patients who had undergone serial pre- and postoperative DTI studies. The first postoperative DTI was performed within 6 months after callosotomy. The second postoperative DTI was performed in five patients with seizure recurrence (symptomatic group) and in seven patients without seizure recurrence (asymptomatic group) after 1 year following surgery. Group comparisons of fractional anisotropy (FA) with age- and sex-matched controls were performed in a whole brain voxel-wise manner using DTI-TBSS.

Results

The first postoperative DTI-TBSS showed a significant FA decrease in the entire corpus callosum in all patients. The second postoperative DTI-TBSS showed that a significant FA decrease remained in the entire corpus callosum in the asymptomatic group. However, in the symptomatic group, no significant decrease of FA was observed in some parts of the posterior body and splenium of the corpus callosum, although there was still a significant FA decrease in the genu of the corpus callosum.

Conclusions

Using DTI-TBSS analysis, we characterized and visualized microstructural white matter changes over time in relation to seizure recurrence in callosotomy patients, suggesting that reorganization of some transected white matter tracts may be related to seizure recurrence. DTI-TBSS analysis can provide reliable and useful information about the state of white matter bundles affected by corpus callosotomy in a noninvasive manner.     

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

Background

In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence.

Methods

DTI was performed in 78 healthy subjects aged 8–21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence.

Results

In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age.

Conclusions

These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.     

Increased white matter integrity in the corpus callosum in subjects with high genetic loading for schizophrenia

Objective

White matter abnormalities in the corpus callosum (CC) of schizophrenia have been reported to predate the illness onset. This study aimed to investigate the effect of genetic predisposition on the white matter integrity of the CC, in subjects at genetically high risk for schizophrenia (GHR) and schizophrenia patients.

Method

Fractional anisotropy (FA) of the mid-sagittal CC in 22 young GHR, 15 schizophrenia, and 26 control subjects were examined. GHR subjects were defined as non-prodromal individuals who had more than two relatives with schizophrenia within third-degree relatives, one of whom must be a first-degree relative.

Results

ANCOVA with age and gender as covariates revealed overall difference of FA in the genu and splenium among the three groups. Post-hoc analysis found significantly increased FA in the genu of GHR subjects compared to controls (corrected p < 0.01), whereas schizophrenia patients showed significantly decreased FA in the splenium.

Conclusion

The white matter change of the CC in young GHR subjects was the opposite of that in schizophrenia. To consider previous reports on FA decrease in the CC in schizophrenia and the impaired frontal functioning in GHR group, the increased FA may be an indicator of compensatory alteration in white matter integrity in young GHR people.     

Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls

Background

Neuregulin1 (NRG1) influences the development of white matter connectivity and is implicated in genetic susceptibility to schizophrenia. The cingulum bundle is a white matter structure implicated in schizophrenia. Its anterior component is especially implicated, as it provides reciprocal connections between brain regions with prominent involvement in the disorder. Abnormalities in the structural integrity of the anterior cingulum in patients with schizophrenia have been reported previously. The present study investigated the potential contribution of NRG1 variation to anterior cingulum abnormalities in participants with schizophrenia.

Methods

We studied 31 men with schizophrenia and 36 healthy men using diffusion tensor imaging to investigate the association between fractional anisotropy in the anterior cingulum and a single-nucleotide polymorphism (SNP8NRG221533: rs35753505) of NRG1.

Results

Consistent with previous reports, fractional anisotropy was significantly reduced in the anterior cingulum in the schizophrenia group. Moreover, the results revealed a significant group (schizophrenia, control) by genotype (C/C, T carriers, including CT and TT) interaction between genetic variation in NRG1 and diagnosis of schizophrenia, such that the patients with the T allele for SNP8NRG221533 had significantly decreased anterior cingulum fractional anisotropy compared with patients homozygous for the C allele and healthy controls who were T carriers.

Limitations

Limitations of our study included the small sample size of the TT subgroup and our use of only fractional anisotropy as an index of myelin integrity. In addition, the use of diffusion tensor imaging acquisition methods limited our ability to study other brain regions that may be involved in schizophrenia.

Conclusion

Our results suggest that NRG1 variation may play a role in the pathophysiology of anterior cingulum abnormalities in patients with schizophrenia.