Regional Abnormality of Grey Matter in Schizophrenia: Effect from the Illness or Treatment?

Both schizophrenia and antipsychotic treatment are known to modulate brain morphology. However, it is difficult to establish whether observed structural brain abnormalities are due to disease or the effects of treatment. The aim of this study was to investigate the effects of illness and antipsychotic treatment on brain structures in antipsychotic-naïve first-episode schizophrenia based on a longitudinal short-term design. Twenty antipsychotic-naïve subjects with first-episode schizophrenia and twenty-four age- and sex-matched healthy controls underwent 3T MRI scans. Voxel-based morphometry (VBM) was used to examine the brain structural abnormality in patients compared to healthy controls. Nine patients were included in the follow-up examination after 8 weeks of treatment. Tensor-based morphometry (TBM) was used to identify longitudinal brain structural changes. We observed significantly reduced grey matter volume in the right superior temporal gyrus in antipsychotic-naïve patients with schizophrenia compared with healthy controls. After 8 weeks of treatment, patients showed significantly increased grey matter volume primarily in the bilateral prefrontal cortex, insula, right thalamus, left superior occipital cortex and the bilateral cerebellum. In addition, a greater enlargement of the prefrontal cortex is associated with the improvement in negative symptoms, and a more enlarged thalamus is associated with greater improvement in positive symptoms. Our results suggest the following: (1) the abnormality in the right superior temporal gyrus is present in the early stages of schizophrenia, possibly representing the core region related to schizophrenia; and (2) atypical antipsychotics could modulate brain morphology involving the thalamus, cortical grey matter and cerebellum. In addition, examination of the prefrontal cortex and thalamus might facilitate an efficient response to atypical antipsychotics in terms of symptom improvement.     

Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Na?ve Patients with Obsessive-Compulsive Disorder

Background

Obsessive-compulsive disorder (OCD) is a mental illness characterized by the loss of control. Because the cingulate cortex is believed to be important in executive functions, such as inhibition, we used functional magnetic resonance imaging (fMRI) techniques to examine whether and how activity and functional connectivity (FC) of the cingulate cortex were altered in drug-naïve OCD patients.

Methods

Twenty-three medication-naïve OCD patients and 23 well-matched healthy controls received fMRI scans in a resting state. Functional connectivities of the anterior cingulate (ACC) and the posterior cingulate (PCC) to the whole brain were analyzed using correlation analyses based on regions of interest (ROI) identified by the fractional amplitude of low-frequency fluctuation (fALFF). Independent Component Analysis (ICA) was used to identify the resting-state sub-networks.

Results

fALFF analysis found that regional activity was increased in the ACC and decreased in the PCC in OCD patients when compared to controls. FC of the ACC and the PCC also showed different patterns. The ACC and the PCC were found to belong to different resting-state sub-networks in ICA analysis and showed abnormal FC, as well as contrasting correlations with the severity of OCD symptoms.

Conclusions

Activity of the ACC and the PCC were increased and decreased, respectively, in the medication-naïve OCD patients compared to controls. Different patterns in FC were also found between the ACC and the PCC with respect to these two groups. These findings implied that the cardinal feature of OCD, the loss of control, may be attributed to abnormal activities and FC of the ACC and the PCC.     

Structural Brain Changes in Chronic Pain Reflect Probably Neither Damage Nor Atrophy

Chronic pain appears to be associated with brain gray matter reduction in areas ascribable to the transmission of pain. The morphological processes underlying these structural changes, probably following functional reorganisation and central plasticity in the brain, remain unclear. The pain in hip osteoarthritis is one of the few chronic pain syndromes which are principally curable. We investigated 20 patients with chronic pain due to unilateral coxarthrosis (mean age 63.25±9.46 (SD) years, 10 female) before hip joint endoprosthetic surgery (pain state) and monitored brain structural changes up to 1 year after surgery: 6–8 weeks, 12–18 weeks and 10–14 month when completely pain free. Patients with chronic pain due to unilateral coxarthrosis had significantly less gray matter compared to controls in the anterior cingulate cortex (ACC), insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex. These regions function as multi-integrative structures during the experience and the anticipation of pain. When the patients were pain free after recovery from endoprosthetic surgery, a gray matter increase in nearly the same areas was found. We also found a progressive increase of brain gray matter in the premotor cortex and the supplementary motor area (SMA). We conclude that gray matter abnormalities in chronic pain are not the cause, but secondary to the disease and are at least in part due to changes in motor function and bodily integration.     

Neural substrate of nicotine addiction as defined by functional brain maps of gene expression

The distributed neural networks involved in the intravenous self-administration of nicotine and cocaine, and in a model of relapse of nicotine-taking after abstinence, were compared in Wistar rats. Post-mortem brain maps of c-fos-related antigens expression showed specific activation in prefrontal cortex, anterior cingulate and nucleus accumbens for both drugs, but of the anterior cingulate cortex only during relapse, suggesting that a subset of the neural network involved in drug self-administration is activated during relapse.     

Morphologic and Functional Connectivity Alterations of Corticostriatal and Default Mode Network in Treatment-Na?ve Patients with Obsessive-Compulsive Disorder

Background

Previous studies have demonstrated that structural deficits and functional connectivity imbalances might underlie the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of the present study was to investigate gray matter deficits and abnormal resting-state networks in patients with OCD and further investigate the association between the anatomic and functional alterations and clinical symptoms.

Methods

Participants were 33 treatment-naïve OCD patients and 33 matched healthy controls. Voxel-based morphometry was used to investigate the regions with gray matter abnormalities and resting-state functional connectivity analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain.

Results

Compared with healthy controls, patients with OCD showed significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex, as well as decreased gray matter volume in the bilateral medial orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal gyrus. By using the above morphologic deficits areas as seed regions, functional connectivity analysis found abnormal functional integration in the cortical-striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent correlation analyses revealed that morphologic deficits in the left thalamus and increased functional connectivity within the CSTC circuits positively correlated with the total Y-BOCS score.

Conclusion

This study provides evidence that morphologic and functional alterations are seen in CSTC circuits and default mode network in treatment-naïve OCD patients. The association between symptom severity and the CSTC circuits suggests that anatomic and functional alterations in CSTC circuits are especially important in the pathophysiology of OCD.     

Verbal Memory Deficits Are Correlated with Prefrontal Hypometabolism in 18FDG PET of Recreational MDMA Users

Introduction

3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users.

Methods

Brain glucose metabolism in rest was assessed using 2-deoxy-2-(¹⁸F)fluoro-D-glucose positron emission tomography (¹⁸FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. ¹⁸FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test.

Results

As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex.

Conclusions

Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined fronto-parieto-mediotemporal dysfunction.     

Structural Modifications of the Brain in Acclimatization to High-Altitude

Adaptive changes in respiratory and cardiovascular responses at high altitude (HA) have been well clarified. However, the central mechanisms underlying HA acclimatization remain unclear. Using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) with fractional anisotropy (FA) calculation, we investigated 28 Han immigrant residents (17–22 yr) born and raised at HA of 2616–4200 m in Qinghai-Tibetan Plateau for at least 17 years and who currently attended college at sea-level (SL). Their family migrated from SL to HA 2–3 generations ago and has resided at HA ever since. Control subjects were matched SL residents. HA residents (vs. SL) showed decreased grey matter volume in the bilateral anterior insula, right anterior cingulate cortex, bilateral prefrontal cortex, left precentral cortex, and right lingual cortex. HA residents (vs. SL) had significantly higher FA mainly in the bilateral anterior limb of internal capsule, bilateral superior and inferior longitudinal fasciculus, corpus callosum, bilateral superior corona radiata, bilateral anterior external capsule, right posterior cingulum, and right corticospinal tract. Higher FA values in those regions were associated with decreased or unchanged radial diffusivity coinciding with no change of longitudinal diffusivity in HA vs. SL group. Conversely, HA residents had lower FA in the left optic radiation and left superior longitudinal fasciculus. Our data demonstrates that HA acclimatization is associated with brain structural modifications, including the loss of regional cortical grey matter accompanied by changes in the white matter, which may underlie the physiological adaptation of residents at HA.     

Frontal-Subcortical Volumetric Deficits in Single Episode,Medication-Na?ve Depressed Patients and the Effects of 8 Weeks Fluoxetine Treatment: A VBM-DARTEL Study

Background

Convergent studies suggest that morphological abnormalities of frontal-subcortical circuits which involved with emotional and cognitive processing may contribute to the pathophysiology of major depressive disorder (MDD). Antidepressant treatment which has been reported to reverse the functional abnormalities of frontal-subcortical circuits in MDD may have treating effects to related brain morphological abnormalities. In this study, we used voxel-based morphometry method to investigate whole brain structural abnormalities in single episode, medication-naïve MDD patients. Furthermore, we investigated the effects of an 8 weeks pharmacotherapy with fluoxetine.

Methods

28 single episode, medication-naïve MDD participants and 28 healthy controls (HC) acquired the baseline high-resolution structural magnetic resonance imaging (sMRI) scan. 24 MDD participants acquired a follow-up sMRI scan after 8 weeks antidepressant treatment. Gray matter volumetric (GMV) difference between groups was examined.

Results

Medication-naïve MDD had significantly decreased GMV in the right dorsolateral prefrontal cortex and left middle frontal gyrus as well as increased GMV in the left thalamus and right insula compared to HC (P<0.05, corrected). Moreover, treated MDD had significantly increased GMV in the left middle frontal gyrus and right orbitofrontal cortex compared to HC (P<0.05, corrected). No difference on GMV was detected between medication-naïve MDD group and treated MDD group.

Conclusions

This study of single episode, medication-naïve MDD subjects demonstrated structural abnormalities of frontal-subcortical circuitsin the early stage of MDD and the effects of 8 weeks successful antidepressant treatment, suggesting these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.     

Adenosine A2A Receptors Measured with [11C]TMSX PET in the Striata of Parkinson's Disease Patients

Adenosine A_2A receptors (A2ARs) are thought to interact negatively with the dopamine D₂ receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson''s disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-¹¹C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.     

Antidepressant treatment normalizes white matter volume in patients with major depression

Objective

To investigate white matter volume abnormalities in patients with major depression and the effects of antidepressant treatment on white matter volume.

Method

Magnetic resonance imaging (MRI) was performed on 32 treatment-naïve depressed patients, 17 recovered patients who had received antidepressant treatment and subsequently achieved clinical recovery and 34 matched controls.

Results

Relative to the healthy controls, the treatment-naïve depressed patients showed increased white matter volumes in the left dorsolateral prefrontal cortex (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum posterior lobe and left inferior parietal lobule. For the treatment-naïve patients, the length in months of the current depressive episode was positively correlated with the white matter volumes in both the left DLPFC and left putamen. In the recovered patients, the differences in white matter volume were no longer statistically significant relative to healthy controls. No significant difference was found in the total white matter volume among the three groups.

Conclusions

This study demonstrates that there were alterations in the white matter volumes of depressed patients, which might disrupt the neural circuits that are involved in emotional and cognitive function and thus contribute to the pathophysiology of depression. The finding of the significant correlations between refractoriness and the white matter volumes in the left DLPFC and left putamen combined with the finding that antidepressant treatment normalized the white matter volume of recovered patients, suggests that a quantitative, structural MRI measurement could act as a potential biomarker in depression therapy for individual subjects.     

Enhanced anxiety observed in cocaine withdrawn rats is associated with altered reactivity of the dorsomedial prefrontal cortex

Discontinuation of drug intake in cocaine abusers commonly produces a variety of adverse withdrawal symptoms among which anxiety and depression-related behavior are prevailing during the initial period of abstinence. The aim of this study was to provide further insight into the neurobiological dysregulations that might contribute to these pathological states. Rats were treated with cocaine or saline for 14 days (20 mg/kg; i.p) and anxiety-related behavior was assessed in different paradigms (elevated plus-maze (EPM), confinement to an open arm of the EPM and shock-probe burying tests) for up to 4 weeks after withdrawal. Depression-like behavior was assessed by the forced swim test and sucrose preference test. Altogether our results demonstrated that cocaine withdrawal induced persistent heightened levels of anxiety that last for at least 28 days but did not affect depression-like behavior. We then used Fos immunohistochemistry to map neuronal activation patterns in withdrawn rats confined to one open arm of an EPM, and a double labeling procedure using Fos immunohistochemistry and in situ hybridization of glutamic acid decarboxylase or vesicular glutamate transporter mRNAs to identify the phenotype of the activated neurons. Our data showed that the exacerbated anxiety observed in cocaine withdrawn rats exposed to an elevated open arm was accompanied by an altered reactivity of the dorsal part of the medial prefrontal cortex (anterior cingulate and dorsal prelimbic cortices), the paraventricular thalamic nucleus and the lateral and anterior areas of the hypothalamus. In the medial prefrontal cortex, we evidenced a negative correlation between Fos expression in its dorsal part and open arm-induced freezing in NaCl-treated rats but not in cocaine withdrawn rats. We also found that more than 65% of activated neurons were glutamatergic projection neurons. The present study provides new insights into the neuroanatomical regions and neuronal cell types that may underlie pathological anxiety during cocaine withdrawal.     

The Self-Liking Brain: A VBM Study on the Structural Substrate of Self-Esteem

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource.     

Cerebral cortical representation of reflexive and volitional swallowing in humans

The purpose of this study was to compare cerebral cortical representation of experimentally induced reflexive swallow with that of volitional swallow. Eight asymptomatic adults (24-27 yr) were studied by a single-trial functional magnetic resonance imaging technique. Reflexive swallowing showed bilateral activity concentrated to the primary sensory/motor regions. Volitional swallowing was represented bilaterally in the insula, prefrontal, cingulate, and parietooccipital regions in addition to the primary sensory/motor cortex. Intrasubject comparison showed that the total volume of activity during volitional swallowing was significantly larger than that activated during reflexive swallows in either hemisphere (P < 0.001). For volitional swallowing, the primary sensory/motor region contained the largest and the insular region the smallest volumes of activation in both hemispheres, and the total activated volume in the right hemisphere was significantly larger compared with the left (P < 0.05). Intersubject comparison showed significant variability in the volume of activity in each of the four volitional swallowing cortical regions. We conclude that reflexive swallow is represented in the primary sensory/motor cortex and that volitional swallow is represented in multiple regions, including the primary sensory/motor cortex, insular, prefrontal/cingulate gyrus, and cuneus and precuneus region. Non-sensory/motor regions activated during volitional swallow may represent swallow-related intent and planning and possibly urge.     

Female Adolescents with Severe Substance and Conduct Problems Have Substantially Less Brain Gray Matter Volume

ObjectiveStructural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Hypotheses: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum).MethodsWe conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold.ResultsFemale adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls.ConclusionsFemale adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.     

Apnea-Induced Cortical BOLD-fMRI and Peripheral Sympathoneural Firing Response Patterns of Awake Healthy Humans

End-expiratory breath-holds (BH) and Mueller manoeuvres (MM) elicit large increases in muscle sympathetic nerve activity (MSNA). In 16 healthy humans (9♀, 35±4 years) we used functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast to determine the cortical network associated with such sympathoexcitation. We hypothesized that increases in MSNA evoked by these simulated apneas are accompanied by BOLD contrast changes in the insular cortex, thalamus and limbic cortex. A series of 150 whole-brain images were collected during 3 randomly performed 16-second end-expiratory BHs and MMs (-30 mmHg). The identical protocol was repeated separately with MSNA recorded from the fibular nerve. The time course of the sympathoexcitatory response to both breathing tasks were correlated with whole-brain BOLD signal changes. Brain sites demonstrating both positive (activation) and negative (deactivation) correlations with the MSNA time course were identified. Sympathetic burst incidence increased (p<0.001) from 29±6 (rest) to 49±6 (BH) and 47±6 bursts/100 heartbeats (MM). Increased neural activity (Z-scores) was identified in the right posterior and anterior insular cortices (3.74, 3.64), dorsal anterior cingulate (3.42), fastigial and dentate cerebellar nuclei (3.02, 3.34). Signal intensity decreased in the left posterior insula (3.28) and ventral anterior cingulate (3.01). Apnea both activates and inhibits elements of a cortical network involved in the generation of sympathetic outflow. These findings identify a neuroanatomical substrate to guide future investigations into central mechanisms contributing to disorders characterized by elevated basal MSNA and exaggerated sympathetic responses to simulated apneas such as sleep apnea and heart failure.     

Long-Term Occupational Stress Is Associated with Regional Reductions in Brain Tissue Volumes

There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM) and white matter (WM) volumes, and the volumes of hippocampus, caudate, and putamen – structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment.     

Neural Basis of Anticipatory Anxiety Reappraisals

Reappraisal is a well-known emotion regulation strategy. Recent neuroimaging studies suggest that reappraisal recruits both medial and lateral prefrontal brain regions. However, few studies have investigated neural representation of reappraisals associated with anticipatory anxiety, and the specific nature of the brain activity underlying this process remains unclear. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with reappraisals of transient anticipatory anxiety. Although transient anxiety activated mainly subcortical regions, reappraisals targeting the anxiety were associated with increased activity in the medial and lateral prefrontal regions (including the orbitofrontal and anterior cingulate cortices). Reappraisal decreased fear circuit activity (including the amygdala and thalamus). Correlational analysis demonstrated that reductions in subjective anxiety associated with reappraisal were correlated with orbitofrontal and anterior cingulate cortex activation. Reappraisal recruits medial and lateral prefrontal regions; particularly the orbitofrontal and anterior cingulate cortices are associated with successful use of this emotion regulation strategy.     

Grey and White Matter Changes across the Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Continuum

There is increasing evidence that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a clinical, pathological and genetic continuum with patients of one disease exhibiting features of the other. Nevertheless, to date, the underlying grey matter and white matter changes across the ALS-FTD disease continuum have not been explored. In this study fifty-three participants with ALS (n = 10), ALS-FTD (n = 10) and behavioural variant FTD (bvFTD; n = 15) as well as controls (n = 18), underwent detailed clinical assessment plus structural imaging using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis of magnetic resonance brain imaging to examine grey and white matter differences and commonalities across the continuum. Importantly, patient groups were matched for age, education, gender and disease duration. VBM and DTI results showed that changes in the ALS group were confined mainly to the motor cortex and anterior cingulate as well as their underlying white matter tracts. ALS-FTD and bvFTD showed widespread grey matter and white matter changes involving frontal and temporal lobes. Extensive prefrontal cortex changes emerged as a marker for bvFTD compared to other subtypes, while ALS-FTD could be distinguished from ALS by additional temporal lobe grey and white matter changes. Finally, ALS could be mainly distinguished from the other two groups by corticospinal tract degeneration. The present study shows for the first time that FTD and ALS overlap in anterior cingulate, motor cortex and related white matter tract changes across the whole continuum. Nevertheless, frontal and temporal atrophy as well as corticospinal tract degeneration emerged as marker for subtype classification, which will inform future diagnosis and target disease management across the continuum.     

Voxel Based Morphometry Alterations in Mal de Debarquement Syndrome

Background

Mal de debarquement syndrome (MdDS) is a disorder of chronic self-motion perception that occurs though entrainment to rhythmic background motion, such as from sea voyage, and involves the perception of low-frequency rocking that can last for months or years. The neural basis of this persistent sensory perception abnormality is not well understood.

Methods

We investigated grey matter volume differences underlying persistent MdDS by performing voxel-based morphometry on whole brain and pre-specified ROIs in 28 individuals with MdDS and comparing them to 18 age, sex, and handedness matched controls.

Results

MdDS participants exhibited greater grey matter volume in the left inferior parietal lobule, right inferior occipital gyrus (area V3v), right temporal pole, bilateral cerebellar hemispheric lobules VIII/IX and left lobule VIIa/VIIb. Grey matter volumes were lower in bilateral inferior frontal, orbitofrontal, pregenual anterior cingulate cortex (pgACC) and left superior medial gyri (t = 3.0, p<0.005_uncorr). In ROI analyses, there were no volume differences in the middle occipital gyrus (region of V5/MT) or parietal operculum 2 (region of the parietoinsular vestibular cortex). Illness duration was positively related to grey matter volume in bilateral inferior frontal gyrus/anterior insula (IFG/AI), right posterior insula, superior parietal lobule, left middle occipital gyrus (V5/MT), bilateral postcentral gyrus, anterior cerebellum, and left cerebellar hemisphere and vermian lobule IX. In contrast, illness duration was negatively related to volume in pgACC, posterior middle cingulate gyrus (MCC), left middle frontal gyrus (dorsolateral prefrontal cortex-DLPFC), and right cerebellar hemispheric lobule VIIIb (t = 3.0, p<0.005_uncorr). The most significant differences were decreased volume in the pgACC and increased volume in the left IFG/AI with longer illness duration (qFDR_corr <0.05). Concurrent medication use did not correlate with these findings or have a relationship with duration of illness. MdDS participants showed positive correlations between grey matter volume in pgACC and bilateral cerebellar lobules VIII/IX, which was not seen in controls.

Conclusions

Individuals with MdDS show brain volume differences from healthy controls as well as duration of illness dependent volume changes in (a) visual-vestibular processing areas (IPL, SPL, V3, V5/MT), (b) default mode network structures (cerebellar IX, IPL, ACC), (c) salience network structures (ACC and IFG/AI) (d) somatosensory network structures (postcentral gyrus, MCC, anterior cerebellum, cerebellar lobule VIII), and (e) a structure within the central executive network (DLPFC). The identification of these associations may enhance future investigations into how exposure to oscillating environments can modulate brain function and affect motion perception as well cognitive and affective control.