Brain Disconnection Research Articles

Brain disconnections link structural connectivity with function and behaviour

Brain lesions do not just disable but also disconnect brain areas, which once deprived of their input or output, can no longer subserve behaviour and cognition. The role of white matter connections has remained an open question for the past 250 years. Based on 1333 stroke lesions, here we reveal the human Disconnectome and demonstrate its relationship to the functional segregation of the human brain. Results indicate that functional territories are not only defined by white matter connections, but also by the highly stereotyped spatial distribution of brain disconnections. While the former has granted us the possibility to map 590 functions on the white matter of the whole brain, the latter compels a revision of the taxonomy of brain functions. Overall, our freely available Atlas of White Matter Function will enable improved clinical-neuroanatomical predictions for brain lesion studies and provide a platform for explorations in the domain of cognition.

Altered brain structural and functional connectivity in schizotypy.

Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of 'brain disconnection' and 'brain connectivity compensation' to 'brain connectivity decompensation'. In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated. We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network. These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.

Disruption of structural brain networks in Primary Open Angle Glaucoma.

Primary open angle glaucoma (POAG) is one of the most common causes of permanent blindness in the world. Recent studies have originated the hypothesis that POAG could be considered as a central nervous system pathology which results in secondary visual involvement. The aim of this study is to assess possible structural whole brain connectivity alterations in POAG by combining multi-shell diffusion weighted imaging, multi-shell multi-tissue probabilistic tractography, graph theoretical measures and a newly designed disruption index, which evaluates the global reorganization of brain networks in group-wise comparisons. We found global differences in structural connectivity between Glaucoma patients and controls, as well as in local graph theoretical measures. These changes extended well beyond the primary visual pathway. Furthermore, group-wise and subject-wise disruption indices were found to be statistically different between glaucoma patients and controls, with a positive slope. Overall, our results support the hypothesis of a whole-brain structural reorganization in glaucoma which is specific to structural connectivity, possibly placing this disease within the recently defined groups of brain disconnection syndrome.

Analysis of local gyrification index using a novel shape-adaptive kernel and the standard FreeSurfer spherical kernel – evidence from chronic schizophrenia outpatients

Schizophrenia can be considered a brain disconnectivity condition related to aberrant neurodevelopment that causes alterations in the brain structure, including gyrification of the cortex. Literature findings on cortical folding are incoherent: they report hypogyria in the frontal, superior-parietal and temporal cortices, but also frontal hypergyria. This discrepancy in local gyrification index (LGI) results could be due to the commonly used spherical kernel (Freesurfer), which is a method of analysis that is still not spatially precise enough. In this study we would like to test the spatial accuracy of a novel method based on a shape-adaptive kernel (Cmorph). The analysis of differences in gyrification between chronic schizophrenia outpatients (n = 30) and healthy controls (n = 30) was conducted with two methods: Freesurfer LGI and Cmorph LGI. Widespread differences in the LGI between schizophrenia outpatients and healthy controls were found using both methods. Freesurfer showed hypogyria in the superior temporal gyrus and the right temporal pole; it also showed hypergyria in the rostral-middle-frontal cortex in schizophrenia outpatients. In comparison, Cmorph revealed that hypergyria is equally represented as hypogyria in orbitofrontal and central brain regions. The clusters from Cmorph were smaller and distributed more broadly, covering all lobes of the brain. The presented evidence from disrupted cortical folding in schizophrenia indicates that the shape-adaptive kernel approach has a potential to improve the knowledge on the disrupted cortical folding in schizophrenia; therefore, it could be a valuable tool for further investigation on big sample size.

M139. DIFFERENTIAL PATTERNS OF BRAIN METABOLISM IN STABILIZED, ACTIVELY SYMPTOMATIC TREATMENT RESISTANT VS. TREATMENT RESPONDER SCHIZOPHRENIA PATIENTS: A STUDY BY 18F-FDG-POSITRON EMISSION TOMOGRAPHY AND STRUCTURAL 3T MRI

BackgroundSchizophrenia is a disabling psychiatric disease with a lifetime prevalence of 1%, which usually starts in late adolescence or initial adulthood and has a rare possibility of recovery. According to the extent of antipsychotic response, schizophrenia individuals can be divided into treatment resistant schizophrenia (TRS) and Treatment responders (non-TRS). Currently, it is unclear whether these categories belong to different biological and prognostic groups. Therefore, in order to deepen the knowledge of these conditions, we analyzed the cerebral metabolism of a sample of stabilized but still actively symptomatic TRS and non-TRS patients with substantial cognitive deficits.MethodsWe recruited 35 schizophrenia patients (18 TRS and 17 non-TRS) among approximately 80 consecutive non-affective psychotic patients, that were referred to our academic outpatient unit for supposed resistance to antipsychotics. The diagnosis of TRS was made by a structured diagnostic flowchart, according to published guidelines. Patients underwent a wide set of clinical and cognitive evaluations by trained raters. All patients who exhibited substantial cognitive deficits (at least two BACS/MATRICS items < than 1 - adjusted scores) and met inclusion/not met exclusion criteria were included in the neuroimaging study by 18F-fluorodeoxyglucose PET scans and structural 3T Magnetic Resonance Imaging. There were no statistically significant differences in age, chlorpromazine equivalents, and duration of illness between the TRS/non-TRS groups. Patients groups were matched with a control group. PET images were normalized on SPM template and then examined in visual and voxel-based analyses.ResultsGlobally, the visual analysis of the images showed a diffuse relative metabolic reduction in the cerebral cortex with prevalent frontal involvement in the majority of the patients of the TRS group and to a lesser extent in the non-TRS group. The voxel-per-voxel analysis revealed an extensive cluster of significant relative metabolic reduction in TRS patients compared to controls and to non-TRS patients (13653 voxels) localized bilaterally in the frontal cortex with a mild left prevalence. In particular, the metabolic reduction peaks involved the upper right and left medial frontal girder (BA6 and BA8, respectively), left opercular frontal (BA44), middle frontal girth (BA10) bilaterally, left lower frontal girth (BA47). Notably, at least three patients from the TRS group were excluded from the initial pool due to the observation of previously unrecognized structural brain anomalies.DiscussionIn this study, we observed that TRS patients had a relative hypometabolic state in dorsal and medial prefrontal cortex, including frontobasal areas, compared to controls and to non-TRS patients, while the striatum and the occipital cortex appeared relatively preserved. In non-TRS patients, brain distribution of 18F-FDG was more homogeneous and only slightly reduced in the cerebral cortex, as compared to controls.These patterns of brain metabolism cannot be associated with more severe cognitive dysfunctions in TRS patients since all patients included in the study had substantial cognitive impairments, irrespective of being TRS or non-TRS. Although it cannot be excluded that these differential patterns may stem from the lack of response to antipsychotics, our findings suggest distinct neurobiological alterations in TRS vs. non-TRS patients, which may include more relevant brain disconnections in non-responder ones.

Tractography-based classification in distinguishing patients with first-episode schizophrenia from healthy individuals

BackgroundSchizophrenia has been characterized as a neurodevelopmental disorder of brain disconnectivity. However, whether disrupted integrity of white matter tracts in schizophrenia can potentially serve as individual discriminative biomarkers remains unclear. MethodsA random forest algorithm was applied to tractography-based diffusion properties obtained from a cohort of 65 patients with first-episode schizophrenia (FES) and 60 healthy individuals to investigate the machine-learning discriminative power of white matter disconnectivity. Recursive feature elimination was used to select the ultimate white matter features in the classification. Relationships between algorithm-predicted probabilities and clinical characteristics were also examined in the FES group. ResultsThe classifier was trained by 80% of the sample. Patients were distinguished from healthy individuals with an overall accuracy of 71.0% (95% confident interval: 61.1%, 79.6%), a sensitivity of 67.3%, a specificity of 75.0%, and the area under receiver operating characteristic curve (AUC) was 79.3% (χ2 p < 0.001). In validation using the held-up 20% of the sample, patients were distinguished from healthy individuals with an overall accuracy of 76.0% (95% confident interval: 54.9%, 90.6%), a sensitivity of 76.9%, a specificity of 75.0%, and an AUC of 73.1% (χ2 p = 0.012). Diffusion properties of inter-hemispheric fibres, the cerebello-thalamo-cortical circuits and the long association fibres were identified to be the most discriminative in the classification. Higher predicted probability scores were found in younger patients. ConclusionsOur findings suggest that the widespread connectivity disruption observed in FES patients, especially in younger patients, might be considered potential individual discriminating biomarkers.

Schizotypal Traits are Linked to Dopamine-Induced Striato-Cortical Decoupling: A Randomized Double-Blind Placebo-Controlled Study.

The dopamine hypothesis of schizophrenia implies that alterations in the dopamine system cause functional abnormalities in the brain that may converge to aberrant salience attribution and eventually lead to psychosis. Indeed, widespread brain disconnectivity across the psychotic spectrum has been revealed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic spectrum disorders remains partly unclear-in particular at the low-end of the psychosis continuum. Therefore, we investigated dopamine-induced changes in striatal iFC and their modulation by psychometrically assessed schizotypy. Our randomized, double-blind placebo-controlled study design included 54 healthy, right-handed male participants. Each participant was assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 minutes of rs-fMRI scanning. Participants then received either a placebo or 200 mg of L-DOPA, a dopamine precursor. We analyzed iFC of 6 striatal seeds that are known to evoke modulation of dopamine-related networks. The main effect of L-DOPA was a significant functional decoupling from the right ventral caudate to both occipital fusiform gyri. This dopamine-induced decoupling emerged primarily in participants with low SPQ scores, while participants with high positive SPQ scores showed decoupling indifferently of the L-DOPA challenge. Taken together, these findings demonstrate that schizotypal traits may be the result of dopamine-induced striato-occipital decoupling.

Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease

Memory loss is one of the first symptoms of typical Alzheimer's disease (AD), for which there are no effective therapies available. The precuneus (PC) has been recently emphasized as a key area for the memory impairment observed in early AD, likely due to disconnection mechanisms within large-scale networks such as the default mode network (DMN). Using a multimodal approach we investigated in a two-week, randomized, sham-controlled, double-blinded trial the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the PC on cognition, as measured by the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite in 14 patients with early AD (7 females). TMS combined with electroencephalography (TMS-EEG) was used to detect changes in brain connectivity. We found that rTMS of the PC induced a selective improvement in episodic memory, but not in other cognitive domains. Analysis of TMS-EEG signal revealed an increase of neural activity in patients' PC, an enhancement of brain oscillations in the beta band and a modification of functional connections between the PC and medial frontal areas within the DMN.Our findings show that high-frequency rTMS of the PC is a promising, non-invasive treatment for memory dysfunction in patients at early stages of AD. This clinical improvement is accompanied by modulation of brain connectivity, consistently with the pathophysiological model of brain disconnection in AD.

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

L-dopa modulates striatal functional connectivity in adults with psychotic-like experiences: A randomized double-blind placebo-controlled study

IntroductionAccording to the dopamine hypothesis functional brain abnormalities and neurochemical alterations may converge to cause psychosis through aberrant salience attribution. Indeed, resting-state functional magnetic resonance imaging (rs-fMRI) has revealed widespread brain disconnectivity across the psychotic spectrum.ObjectivesTo advance the understanding of the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic disorders we aimed to investigate the link between L-Dopa, a dopamine precursor, and its modulation of striatal iFC in subthreshold psychosis, i.e. non-clinical psychosis.MethodsWe used a randomized, double-blind placebo controlled study design including in our sample 56 healthy, male, right-handed, subjects with no familiar risk factors for psychosis who were assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 minutes of rs-fMRI scanning. All subjects received either 250 mg of Madopar DR®(200 mg L-Dopa plus 50 mg benserazid, dual release form) or a placebo. We analysed resting-state iFC of 6 striatal seeds, known to evoke dopamine related networks.ResultsThe main effect of L-Dopa presented itself (FWE-corrected) as a significant decrease in iFC from the right ventral striatum to the cerebellum and the precuneus cortex, and an increase in iFC to the occipital cortex. Subjects with high SPQ positive symptom sub-scores showed a significant increase of L-Dopa induced connectivity.ConclusionWe identified striatal functional connectivity being modulated by augmented dopamine availability, and in support of the dopamine hypothesis, we found that those iFC patterns are associated to high scores of psychotic like experiences.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Deconstructing the Brain Disconnection-Brain Death Analogy and Clarifying the Rationale for the Neurological Criterion of Death.

This article explains the problems with Alan Shewmon's critique of brain death as a valid sign of human death, beginning with a critical examination of his analogy between brain death and severe spinal cord injury. The article then goes on to assess his broader argument against the necessity of the brain for adult human organismal integration, arguing that he fails to translate correctly from biological to metaphysical claims. Finally, on the basis of a deeper metaphysical analysis, I offer a revised rationale for the validity of the neurological criterion of human death.

Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia.

The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status.

Disrupted connectivity between the salience network and central executive networks in ageing

• Recent work has attributed reduced cognitive abilities arising as a result of healthy ageing to brain disconnection. Understanding this disconnection is important since intact cognition is essential for successful functioning, including perception, attention and memory. • Two widely used methods for studying connectivity are Dynamic Causal Modelling (DCM) and Independent Component Analysis (ICA) • An extension to ICA is to apply stochastic DCM to ICA time courses to study the connectivity between different brain networks • Previous work by Sridharan and colleagues (Sridharan et al., 2008) has suggested that the brain's salience network (SN) is responsible for switching between the default mode network (DMN), the network seen when the brain is at rest, and the central executive network (CEN) • We have previously replicated the work of Sridharan and colleagues in a young cohort and now investigate how this connectivity changes with ageing.

Abstract T P91: Reversion of Cognitive Impairment by Carotid Revascularization in Asymptomatic Carotid Stenosis? A Nonrandomized Controlled Study

We previously reported that patients with asymptomatic severe stenosis of extracranial internal carotid artery (ICA) have worse dizziness and poorer cognitive performance than matched controls in association with distributed and long-range brain disconnections. There is currently a lack of evidence whether optimal medical treatment alone or with carotid revascularization could be the best treatment for cognitive impairment in these patients. We consecutively followed 25 patients with asymptomatic severe stenosis (&gt;70%) of ICA. Sixteen received carotid artery stenting (CAS) and optimal medical treatment and nine received optimal medical treatment alone. All subjects received a battery of neuropsychological tests as well as diffusion tensor imaging and resting-state functional magnetic resonance imaging, and were followed at three months after treatments. We found that patients receiving CAS (100% success), but not those receiving medical treatment alone, had significant improvements in dizziness scores (P=0.001), immediate recall of verbal memory (P=0.002) and complex visuospatial perception (P=0.007) three month after intervention. The interval changes of whole-brain mean fractional anisotropy of both groups were insignificant, and the analysis of functional connectivity is undergoing. The results may provide insight into whether the benefits of carotid revascularization, including mitigating thromboembolic events and cognitive impairment, outweigh perioperative risks including functional consequence of microemboli.

EPA-0137 – EEG power spectra and connectivity changes in animal serotonergic and glutamatergic models of psychosis – implications for treatment

Pharmacological models of psychosis bring a unique tool for studying brain disconnection in humans as well as in animals. Even though several electrophysiological biomarkers have been already described in schizophrenia, little is known about EEG biomarkers in pharmacological models of psychosis and about the translational validity of these data. Studies on EEG brain connectivity in rodents under these circumstances are extremely rare. To elucidate the characteristic patterns of EEG connectivity in freely moving rats we have conducted a series of experiments in serotonergic and glutamatergic models of psychosis. Using multiple cortical electrodes, EEG spectral and connectivity analysis was performed on selected episodes of behavioral inactivity – a model of resting EEG. The analyses showed consistent changes that were specific for each of the models used. Glutamatergic models with ketamine and dizocilpin (MK-801) induced typical global increase in high frequency oscillations. On the contrary, in serotonergic models (psilocin, mescaline, LSD, DOB, 2C-B) a global power decrease was observed. A common denominator in both models was a global decrease in connectivity expressed as decreased coherence in most of the frequency bands. A translational validity of these findings is supported by findings in schizophrenia patients and by recent human studies with ketamine and psilocybin. Recently obtained results with drugs modulating serotonergic, dopaminergic and glutamatergic neurotransmission will be also discussed in the light of potential therapeutic implications. This work was supported by projects IGA MH CZ NT/13897 and DRO (PCP, 00023752), MI CZ VG20122015080 and VG20122015075, ECGA 278006.

58. Cortical sources of resting state EEG rhythms in Alzheimer’s disease patients are related to the integrity of structural brain connectivity as revealed by tractography: An EEG-DTI combined study

Alzheimer’s disease (AD) patients show abnormal cortical sources of resting state EEG rhythms, especially at delta (1–4 Hz) and alpha (8–13 Hz) bands. Here we hypothesized that this abnormality is correlated to impaired structural brain connectivity. Eyes closed resting state EEG and structural MRI-DTI (diffusion tensor imaging) data were acquired in 21 AD and in 9 mild cognitive impairment (MCI) patients. LORETA and FSL were used for data analysis. Compared to MCI subjects, AD patients showed a reduction of DTI fractional anisotropy (FA) in several white matter brain bundles (p < 0.05 corrected). Among these bundles, there was a negative correlation in AD patients between delta sources and FA in Forceps minor, left Superior longitudinal fasciculus, and bilateral Inferior longitudinal fasciculus (p < 0.05 corrected). Analogously, there was a positive correlation in AD patients between alpha sources and FA in Forceps minor, right Superior longitudinal, and left Inferior longitudinal fasciculus (p < 0.05 corrected). In AD patients, abnormal cortical sources of delta and alpha rhythms are correlated to the atrophy of structural long-tract brain connectivity. Cortical sources of resting state EEG rhythms in AD patients reflect a neurodegenerative brain disconnection.

How we fall asleep: regional and temporal differences in electroencephalographic synchronization at sleep onset

ObjectivesWe hypothesized that the brain shows specific and predictable patterns of spatial and temporal differences during sleep onset (SO) reflecting a temporal uncoupling of electrical activity between different cortical regions and a dissociated wakelike and sleeplike electrocortical activity in different cortical areas. MethodsWe analyzed full-scalp electroencephalographic (EEG) recordings of 40 healthy subjects to investigate spatial and temporal changes of EEG activity across the wake-sleep transition. We quantified EEG sleep recordings by a fast Fourier transform (FFT) algorithm and by a better oscillation (BOSC) detection method to the EEG signals, which measured oscillatory activity within a signal containing a nonrhythmic portion. ResultsThe most representative spatial change at SO is the frontalization of slow-wave activity (SWA), while the θ activity, which mostly shares a similar temporal and spatial pattern with SWA, exhibits a temporo-occipital diffusion. The time course of these oscillations confirms that the changes of the dominant waves coexist with topographic changes. The waking occipital prevalence of α oscillations is progressively replaced by an occipital prevalence of θ oscillations. On the other hand, more anterior areas show a wide synchronization pattern mainly expressed by slow waves just below 4Hz and by spindle oscillations. ConclusionsThe whole pattern of results confirms that the centrofrontal areas showed an earlier synchronization (i.e., they fall asleep first). This finding implies a coexistence of wakelike and sleeplike electrical activity during sleep in different cortical areas. It also implies that the process of progressive brain disconnection from the external world as we fall asleep does not necessarily affect primary and higher-order cortices at the same time.

Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis

Background: Brain disconnection plays a major role in determining cognitive disabilities in multiple sclerosis (MS). We recently developed a novel diffusion-weighted magnetic resonance imaging (DW-MRI) tractography approach, namely anatomical connectivitity mapping (ACM), that quantifies structural brain connectivity. Objective: Use of ACM to assess structural connectivity modifications in MS brains and ascertain their relationship with the patients’ Paced-Auditory-Serial-Addition-Test (PASAT) scores. Methods: Relapsing–remitting MS (RRMS) patients (n = 25) and controls (n = 25) underwent MRI at 3T, including conventional images, T1-weighted volumes and DW-MRI. Volumetric scans were coregistered to fractional anisotropy (FA) images, to obtain parenchymal FA maps for both white and grey matter. We initiated probabilistic tractography from all parenchymal voxels, obtaining ACM maps by counting the number of streamlines passing through each voxel, then normalizing by the total number of streamlines initiated. The ACM maps were transformed into standard space, for statistical use. Results: RRMS patients had reduced grey matter volume and FA, consistent with previous literature. Also, we showed reduced ACM in the thalamus and in the head of the caudate nucleus, bilaterally. In our RRMS patients, ACM was associated with PASAT scores in the corpus callosum, right hippocampus and cerebellum. Conclusions: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.

Assessing Corpus Callosum Changes in Alzheimer's Disease: Comparison between Tract-Based Spatial Statistics and Atlas-Based Tractography

Tractography based on Diffusion Tensor Imaging (DTI) represents a valuable tool for investigating brain white matter (WM) microstructure, allowing the computation of damage-related diffusion parameters such as Fractional Anisotropy (FA) in specific WM tracts. This technique appears relevant in the study of pathologies in which brain disconnection plays a major role, such as, for instance, Alzheimer's Disease (AD). Previous DTI studies have reported inconsistent results in defining WM abnormalities in AD and in its prodromal stage (i.e., amnestic Mild Cognitive Impairment; aMCI), especially when investigating the corpus callosum (CC). A reason for these inconsistencies is the use of different processing techniques, which may strongly influence the results. The aim of the current study was to compare a novel atlas-based tractography approach, that sub-divides the CC in eight portions, with Tract-Based Spatial Statistics (TBSS) when used to detect specific patterns of CC FA in AD at different clinical stages. FA data were obtained from 76 subjects (37 with mild AD, 19 with aMCI and 20 elderly healthy controls, HC) and analyzed using both methods. Consistent results were obtained for the two methods, concerning the comparisons AD vs. HC (significantly reduced FA in the whole CC of AD patients) and AD vs. aMCI (significantly reduced FA in the frontal portions of the CC in AD patients), thus identifying a relative preservation of the frontal CC regions in aMCI patients compared to AD. Conversely, the atlas-based method but not the TBSS showed the ability to detect a selective FA change in the CC parietal, left temporal and occipital regions of aMCI patients compared to HC. This finding indicates that an analysis including a higher number of voxels (with no restriction to tract skeletons) may detect characteristic pattern of FA in the CC of patients with preclinical AD, when brain atrophy is still modest.

Impaired pantomime in schizophrenia: Association with frontal lobe function

IntroductionGestures are important for nonverbal communication and were shown to be impaired in schizophrenia. Two categories of gestures can be differentiated: pantomime on verbal command and imitation of seen gestures. There is evidence that the neural basis of these domains may be distinct, pantomime being critically dependent on prefrontal cortex function. The aim of the study was to investigate gestural deficits in schizophrenia and their association with frontal lobe function and motor performance. MethodsIn 30 schizophrenia patients, gesture performance was assessed by the comprehensive Test of Upper Limb Apraxia (TULIA) using previously determined cut-off scores. The ratings of videotaped gesture performance were blinded. In addition, a battery of rating scales on frontal lobe function, parkinsonism, dyskinesia, catatonia and instrumental measures of gross and fine motor performance were assessed. ResultsPantomime deficits were found in 40% and imitation deficits in 23% of the patients. Patients with gestural deficits had poorer frontal cortex function, more catatonic symptoms, and more severe psychopathology. Furthermore, trends indicated an association with a more chronic course of the illness. Pantomime was linked to frontal lobe function whereas imitation was associated with catatonic symptoms and gross motor performance. ConclusionsPantomime is frequently impaired in chronic schizophrenia and may critically depend on motor planning, reflecting a further example of brain disconnectivity in schizophrenia.