Analyzing fractal dimension in electroconvulsive therapy: Unraveling complexity in structural and functional neuroimaging.

BACKGROUND: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. METHODS: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. RESULTS: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. CONCLUSION: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

The Effect of Electroconvulsive Therapy on Specific Catatonia Symptoms and Predictors of Late Response.

INTRODUCTION: Electroconvulsive therapy (ECT) is known to be effective in the treatment of catatonia, reaching response rates of about 80 to 100%. It is indicated in cases of treatment resistance to benzodiazepines and in life-threatening conditions such as malignant catatonia. Beneficial effects on specific symptoms or predictors of response are less clear. The objective of this retrospective study is to examine the ECT effect on specific catatonia symptoms in the acute phase of the illness and to identify predictors of response. METHODS: A retrospective study examined data from 20 patients with catatonia, 18 associated with schizophrenia and 2 with bipolar disorder, who underwent ECT from 2008 to 2021. Ten subjects had more than one ECT-series, resulting in a total of 31 ECT-series. Catatonia symptom severity was assessed with the Bush Francis Catatonia Rating Scale (BFCRS). RESULTS: ECT yielded excellent response. Nineteen of 20 patients and 30 of 31 ECT-series achieved response. The mean number of ECT sessions to response was 4.2. Response to ECT was more pronounced for motor inhibition symptoms such as stupor and mutism, while echophenomena, dyskinesia, stereotypy and perseveration responded less well. A predictor of late response was the presence of grasp reflex. DISCUSSION: The present study corroborates the high and rapid effectiveness of ECT in the treatment of catatonia. Focus on single catatonia signs may help to identify those who are most likely to achieve remission quickly, as well as those who might need longer ECT-series.

Associations of thalamocortical networks with reduced mindfulness in alcohol use disorder.

Background: Increased mindfulness is associated with reduced alcohol consumption in patients with alcohol use disorder (AUD) after residential treatment. However, the underlying neurobiological mechanism of mindfulness in AUD is unclear. Therefore, we investigate the structural and functional alterations of the thalamocortical system with a focus on the mediodorsal thalamic nucleus (MD-TN), the default mode and the salience network (DMN/SN) which has previously been associated with mindfulness in healthy subjects. We hypothesized lower mindfulness and reduced structural and functional connectivity (FC) of the thalamocortical system, particularly in the DMN/SN in AUD. We assumed that identified neurobiological alterations in AUD are associated with impairments of mindfulness. Methods: Forty-five abstinent patients with AUD during residential treatment and 20 healthy controls (HC) were recruited. Structural and resting-state functional MRI-scans were acquired. We analysed levels of mindfulness, thalamic volumes and network centrality degree of the MD-TN using multivariate statistics. Using seed-based whole brain analyses we investigated functional connectivity (FC) of the MD-TN. We performed exploratory correlational analyses of structural and functional DMN/SN measurements with levels of mindfulness. Results: In AUD we found significantly lower levels of mindfulness, lower bilateral thalamic and left MD-TN volumes, reduced FC between MD-TN and anterior cingulum/insula and lower network centrality degree of the left MD-TN as compared to HC. In AUD, lower mindfulness was associated with various reductions of structural and functional aspects of the MD-TN. Conclusion: Our results suggest that structural and functional alterations of a network including the MD-TN and the DMN/SN underlies disturbed mindfulness in AUD.

Electroconvulsive therapy induces remodeling of hippocampal co-activation with the default mode network in patients with depression.

INTRODUCTION: Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.

Distinct and shared patterns of brain plasticity during electroconvulsive therapy and treatment as usual in depression: an observational multimodal MRI-study.

Electroconvulsive therapy (ECT) is a highly effective treatment for depression. Previous studies point to ECT-induced volume increase in the hippocampi and amygdalae, and to increase in cortical thickness. However, it is unclear if these neuroplastic changes are associated with treatment response. This observational study aimed to address this research question by comparing neuroplasticity between patients with depression receiving ECT and patients with depression that respond to treatment as usual (TAU-responders). Twenty ECT-patients (16 major depressive disorder (MDD), 4 depressed bipolar disorder), 20 TAU-responders (20 MDD) and 20 healthy controls (HC) were scanned twice with multimodal magnetic resonance imaging (structure: MP2RAGE; perfusion: arterial spin labeling). ECT-patients were scanned before and after an ECT-index series (ECT-group). TAU-responders were scanned during a depressive episode and following remission or treatment response. Volumes and cerebral blood flow (CBF) of the hippocampi and amygdalae, and global mean cortical thickness were compared between groups. There was a significant group × time interaction for hippocampal and amygdalar volumes, CBF in the hippocampi and global mean cortical thickness. Hippocampal and amygdalar enlargements and CBF increase in the hippocampi were observed in the ECT-group but neither in TAU-responders nor in HC. Increase in global mean cortical thickness was observed in the ECT-group and in TAU-responders but not in HC. The co-occurrence of increase in global mean cortical thickness in both TAU-responders and in ECT-patients may point to a shared mechanism of antidepressant response. This was not the case for subcortical volume and CBF increase.

Reduced structural connectivity of the amygdala is associated with childhood trauma in adult patients with alcohol use disorder.

Childhood trauma (CT) is frequent in patients with alcohol use disorder (AUD) and may impact on adult drinking behaviour and treatment outcome. This study aimed to investigate the structural correlates of CT in AUD, focusing on the amygdala, which plays a crucial role in the neurobiology of trauma. We hypothesized reduced amygdala volume and reduced structural connectivity as quantified by fractional anisotropy (FA) and by number of streamlines in those AUD patients with a history of moderate to severe CT (AUD-CT). T1-weighted MP2RAGE and diffusion-weighted imaging (DWI) 3-Tesla MRI-scans were acquired in 41 recently abstinent patients with AUD. We compared bilateral amygdala volume and structural connectivity (FA and number of streamlines) of pathways emanating from the amygdala between AUD-CT (n = 20) and AUD without CT (AUD-NT, n = 21) using a mixed model multivariate analysis of variance (MANCOVA) controlling for age and gender. AUD-CT displayed reduced FA and reduced number of streamlines of amygdalar tracts. There were no differences regarding amygdala volume. The severity of physical abuse, a subscale of the childhood trauma questionnaire, was negatively correlated with FA and with number of streamlines. AUD-CT and AUD-NT differ regarding structural connectivity of pathways projecting to and from the amygdala, but not regarding amygdala volume. Those alterations of structural connectivity in AUD-CT may represent a distinguishable neurobiological subtype of AUD, which might be associated with the complex clinical picture and poorer outcome that patients with CT and AUD often present.

The role of head circumference and cerebral volumes to phenotype male adults with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) has been repeatedly associated with enlargements of head circumference in children with ASD. However, it is unclear if these enlargements persist into adulthood. This is the first study to investigate head circumference in a large sample of adults with ASD. METHODS: We apply a fully automated magnetic resonance imaging (MRI) based measurement approach to compute head circumference by combining 3D and 2D image processing. Head circumference was compared between male adults with ASD (n = 120) and healthy male controls (n = 136), from the Autism Brain Imaging Data Exchange (ABIDE) database. To explain which brain alterations drive our results, secondary analyses were performed for 10 additional morphological brain metrics. RESULTS: ASD subjects showed an increase in head circumference (p = .0018). In addition, ASD patients had increased ventricular surface area (SA) (p = .0013). Intracranial volume, subarachnoidal cerebrospinal fluid (CSF) volume, and gray matter volume explained 50% of head circumference variance. Using a linear support vector machine, we gained an ASD classification accuracy of 73% (sensitivity 92%, specificity 68%) using head circumference and brain-morphological metrics as input features. Head circumference, ventricular SA, ventricular CSF volume, and ventricular asymmetry index contributed to 85% of feature weighting relevant for classification. CONCLUSION: Our results suggest that head circumference increases in males with ASD persist into adulthood. Results may be driven by morphological alterations of ventricular CSF. The presented approach for an automated head circumference measurement allows for the retrospective investigation of large MRI datasets in neuropsychiatric disorders.

Link between structural connectivity of the medial forebrain bundle, functional connectivity of the ventral tegmental area, and anhedonia in unipolar depression.

The ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) are essential for experiencing pleasure and initiating motivated behaviour. The VTA, NAcc, and PFC are connected through the medial forebrain bundle (MFB). In humans, two branches have been described: an infero-medial branch (imMFB) and a supero-lateral branch (slMFB). This study aimed to explore the associations between structural connectivity of the MFB, functional connectivity (FC) of the VTA, anhedonia, and depression severity in patients with depression. Fifty-six patients with unipolar depression and 22 healthy controls matched for age, sex, and handedness were recruited at the University Hospital of Psychiatry and Psychotherapy in Bern, Switzerland. Diffusion-weighted imaging and resting-state functional magnetic resonance imaging scans were acquired. Using manual tractography, the imMFB and slMFB were reconstructed bilaterally for each participant. Seed-based resting-state FC was computed from the VTA to the PFC. Hedonic tone was assessed using the Fawcett-Clark Pleasure Scale. We identified reduced tract volume and reduced number of tracts in the left slMFB. There was an increase in FC between the VTA and right medial PFC in patients with depression. Depression severity was associated with reduced tract volume and fewer tracts in the left slMFB. Reduced hedonic tone was associated with reduced tract volume. Conversely, reduced hedonic tone was associated with increased FC between the VTA and the PFC. In conclusion, our results suggest reduced structural connectivity of the slMFB in patients with depression. Increases in FC between the VTA and PFC may be associated with anhedonia or compensatory hyperactivity.

Associations between anterior cingulate thickness, cingulum bundle microstructure, melancholia and depression severity in unipolar depression.

BACKGROUND: Structural and functional alterations of the anterior cingulate cortex (ACC) have been related to emotional, cognitive and behavioral domains of major depressive disorder. In this study, we investigate cortical thickness of rostral and caudal ACC. In addition, we explore white matter microstructure of the cingulum bundle (CB), a white matter pathway connecting multiple segments of the ACC. We hypothesized reduced cortical thickness and reduced white matter microstructure of the CB in MDD, in particular in the melancholic subtype. In addition, we expect an association between depression severity and CB microstructure. METHODS: Fifty-four patients with a current depressive episode and 22 healthy controls matched for age, gender and handedness underwent structural and diffusion-weighted MRI-scans. Cortical thickness of rostral and caudal ACC were computed. The CB was reconstructed bilaterally using manual tractography. Cortical thickness and fractional anisotropy (FA) of bilateral CB were compared first between all patients and healthy controls and second between healthy controls, melancholic and non-melancholic patients. Correlations between FA and depression severity were calculated. RESULTS: We found no group differences in rostral and caudal ACC cortical thickness or in FA of the CB comparing all patients with healthy controls. Melancholic patients had reduced cortical thickness of bilateral caudal ACC compared to non-melancholic patients and compared to healthy controls. Across all patients, depression severity was associated with reduced FA in bilateral CB. LIMITATIONS: Impact of medication CONCLUSIONS: Cortical thickness of the caudal ACC is associated with the melancholic syndrome. CB microstructure may represent a marker of depression severity.

Neurological Soft Signs Are Associated With Altered White Matter in Patients With Schizophrenia.

Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.

The role of the orbitofrontal cortex and the nucleus accumbens for craving in alcohol use disorder.

This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD.

Long-Term Outcome and Neuroimaging of Deep Brain Stimulation in Holmes Tremor: A Case Series.

BACKGROUND: Different deep brain stimulation (DBS) targets have been suggested as treatment for patients with pharmacologically refractory Holmes tremor (HT). We report the clinical and quality of life (QoL) long-term (up to nine years) outcome in four patients with HT treated with DBS (in thalamic ventral intermediate nucleus-VIM or in dentato-rubro-thalamic tract-DRTT). MATERIALS AND METHODS: The patients underwent routine clinical evaluations before and after DBS (typically annually). Tremor severity and activities of daily living (ADL) were quantified by the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTMTRS). QoL was assessed using the RAND SF-36-item Health Survey (RAND SF-36). In addition, we computed, in all four patients, the VTA based on the best stimulation settings using heuristic approaches included in the open source toolbox LEAD-DBS. RESULTS: In all patients, tremor and ADL improved significantly at one-year post-DBS follow-up (34-61% improvement in FTMTRS total score compared to baseline). In three out of four patients, the improvement of tremor was sustained no longer than two to three years and only in one patient was sustained up to nine years. In this patient, the largest intersection between VTA and DBS target has been observed. Scores for ADL deteriorated over the course of time, reaching worse levels compared to baseline already during the three-year post-DBS follow-up, in three out of four patients. Physical and mental health component scores of RAND SF-36 had very different outcome between patients and follow-ups and were not associated with tremor-related outcomes. CONCLUSIONS: The benefits of DBS in HT might not be always long lasting. Although QoL slightly improved, this change seemed to be independent of the motor outcome following DBS. The estimation of DBS target and VTA proximity could be a useful tool for DBS clinicians in order to facilitate the DBS programming process and optimize DBS treatment.

Reduced tract length of the medial forebrain bundle and the anterior thalamic radiation in bipolar disorder with melancholic depression.

BACKGROUND: The supero-lateral medial forebrain bundle (slMFB) and the anterior thalamic radiation (ATR) play a core role in reward anticipation and motivational processes. In this study, the slMFB and the ATR were investigated in a group of depressed bipolar disorder (BD) and in healthy controls (HC) using tract length as a measure of fibre geometry and fractional anisotropy (FA) as a measure of white matter microstructure. We hypothesized reduced tract length and FA of the slMFB and the ATR in BD. We expect alterations to be driven by the melancholic subtype. METHODS: Nineteen depressed patients with BD and 19 HC matched for age and gender underwent diffusion-weighted magnetic resonance imaging (MRI) scans. Diffusion tensor imaging (DTI) based tractography was used to reconstruct bilateral slMFB and ATR. Mean tract length and FA were computed for the slMFB and the ATR. Mixed-model ANCOVAs and post-hoc ANCOVAs, controlling for age and intracranial volume, were used to compare tract length and FA of bilateral slMFB and ATR between HC and BD and between HC and subgroups with melancholic and non-melancholic symptoms. RESULTS: In BD we found a significantly shortened tract length of the right slMFB and ATR in BD compared to HC. Subgroup analyses showed that these findings were driven by the melancholic subgroup. Mean-FA did not differ between HC and BD. LIMITATIONS: Sample size CONCLUSIONS: Tract length of the right slMFB and the right ATR is reduced in BD. Those changes of fibre geometry are driven by the melancholic subtype.

Increased structural connectivity of the medial forebrain bundle in schizophrenia spectrum disorders is associated with delusions of paranoid threat and grandiosity.

In many cases delusions in schizophrenia spectrum disorders (SSD) are driven by strong emotions such as feelings of paranoia or grandiosity. We refer to these extreme emotional experiences as psychotic affectivity. We hypothesized that increased structural connectivity of the supero-lateral medial forebrain bundle (slMFB), a major tract of the reward system, is associated with delusional psychotic affectivity. Forty-six patients with SSD and 44 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. The slMFB and a comparison tract (corticospinal tract) were reconstructed using diffusion tensor imaging (DTI)-based tractography. Fractional anisotropy (FA) was sampled across the tracts. We used a mixed-model analyses of variance controlling for age and gender to compare FA of bilateral slMFB between SSD-patients and HC. Correlations of FA of bilateral slMFB and the PANSS-positive item delusions were calculated. In addition, FA was compared between three clinically homogeneous SSD-subgroups in terms of psychotic affectivity (severe, mild and no PA, sPA, mPA, nPA) and HC. FA of the slMFB did not differ between all SSD-patients and HC. In SSD-patients there was a positive correlation between delusions and FA in bilateral slMFB. Likewise, SSD-subgroups of psychotic affectivity and HC differed significantly in FA of the slMFB. Results were driven by higher FA in the right slMFB in sPA as compared to nPA and to HC. There was no significant effect for the comparison tract. In conclusion, increased structural connectivity of the slMFB may underlie delusional experiences of paranoia and grandiosity in SSD.

Physical activity is associated with left corticospinal tract microstructure in bipolar depression.

Psychomotor retardation and reduced daily activities are core features of the depressive syndrome including bipolar disorder (BD). It was the aim of this study to investigate white matter microstructure of the motor system in BD during depression and its association with motor activity. We hypothesized reduced physical activity, microstructural alterations of motor tracts and different associations between activity levels and motor tract microstructure in BD. Nineteen bipolar patients with a current depressive episode (BD) and 19 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. Quantitative motor activity was assessed with 24 h actigraphy recordings. Bilateral corticospinal tracts (CST), interhemispheric connections between the primary motor cortices (M1) and between the pre-supplementary motor areas (pre-SMA) were reconstructed individually based on anatomical landmarks using Diffusion Tensor Imaging (DTI) based tractography. Mean fractional anisotropy (FA) was sampled along the tracts. To enhance specificity of putative findings a segment of the optic radiation was reconstructed as comparison tract. Analyses were complemented with Tract Based Spatial Statistics (TBSS) analyses. BD had lower activity levels (AL). There was a sole increase of fractional anisotropy (FA) in BD in the left CST. Further, there was a significant group x AL interaction for FA of the left CST pointing to a selective positive association between FA and AL in BD. The comparison tract and TBSS analyses did not detect significant group differences. Our results point to white matter microstructure alterations of the left CST in BD. The positive association between motor activity and white matter microstructure suggests a compensatory role of the left CST for psychomotor retardation in BD.

Multimodal Brain Imaging Reveals Structural Differences in Alzheimer's Disease Polygenic Risk Carriers: A Study in Healthy Young Adults.

BACKGROUND: Recent genome-wide association studies have identified genetic loci that jointly make a considerable contribution to risk of developing Alzheimer's disease (AD). Because neuropathological features of AD can be present several decades before disease onset, we investigated whether effects of polygenic risk are detectable by neuroimaging in young adults. We hypothesized that higher polygenic risk scores (PRSs) for AD would be associated with reduced volume of the hippocampus and other limbic and paralimbic areas. We further hypothesized that AD PRSs would affect the microstructure of fiber tracts connecting the hippocampus with other brain areas. METHODS: We analyzed the association between AD PRSs and brain imaging parameters using T1-weighted structural (n = 272) and diffusion-weighted scans (n = 197). RESULTS: We found a significant association between AD PRSs and left hippocampal volume, with higher risk associated with lower left hippocampal volume (p = .001). This effect remained when the APOE gene was excluded (p = .031), suggesting that the relationship between hippocampal volume and AD is the result of multiple genetic factors and not exclusively variability in the APOE gene. The diffusion tensor imaging analysis revealed that fractional anisotropy of the right cingulum was inversely correlated with AD PRSs (p = .009). We thus show that polygenic effects of AD risk variants on brain structure can already be detected in young adults. CONCLUSIONS: This finding paves the way for further investigation of the effects of AD risk variants and may become useful for efforts to combine genotypic and phenotypic data for risk prediction and to enrich future prevention trials of AD.

Increased fractional anisotropy in the motor tracts of Parkinson's disease suggests compensatory neuroplasticity or selective neurodegeneration.

OBJECTIVE: To determine the differences in motor pathways and selected non-motor pathways of the basal ganglia in Parkinson's disease (PD) patients compared to healthy controls (HCs). METHODS: We analysed diffusion weighted imaging data of 24 PD patients and 26 HCs. We performed deterministic tractography analysis using the spherical deconvolution-based damped Richardson-Lucy algorithm and subcortical volume analysis. RESULTS: We found significantly increased fractional anisotropy (FA) in the motor pathways of PD patients: the bilateral corticospinal tract (right; corrected p = 0.0003, left; corrected p = 0.03), bilateral thalamus-motor cortex tract (right; corrected p = 0.02, left; corrected p = 0.004) and the right supplementary area-putamen tract (corrected p = 0.001). We also found significantly decreased FA in the right uncinate fasiculus (corrected p = 0.01) and no differences of FA in the bilateral supero-lateral medial forebrain bundles (p > 0.05) of PD patients compared to HCs. There were no subcortical volume differences (p > 0.05) between the PD patients and HCs. CONCLUSION: These results can inform biological models of neurodegeneration and neuroplasticity in PD. We suggest that increased FA values in the motor tracts in PD may reflect compensatory reorganization of neural circuits indicative of adaptive or extended neuroplasticity. KEY POINTS: • Fractional anisotropy was higher in motor pathways of PD patients compared to healthy controls. • Fractional anisotropy was lower in the uncinate fasciculus of PD patients compared to healthy controls. • Increased fractional anisotropy could suggest adaptive neuroplasticity or selective neurodegeneration.

Myelination of the right parahippocampal cingulum is associated with physical activity in young healthy adults.

Recent evidence suggests that individual differences in physical activity (PA) may be associated with individual differences in white matter microstructure and with grey matter volume of the hippocampus. Therefore, this study investigated the association between PA and white matter microstructure of pathways connecting to the hippocampus. A total of 33 young, healthy adults underwent magnetic resonance imaging (MRI). High angular resolution diffusion-weighted imaging and multi-component relaxometry MRI scans (multi-component driven equilibrium pulse observation of T1 and T2) were acquired for each participant. Activity levels (AL) of participants were calculated from 72-h actigraphy recordings. Tractography using the damped Richardson Lucy algorithm was used to reconstruct the fornix and bilateral parahippocampal cinguli (PHC). The mean fractional anisotropy (FA) and the myelin water fraction (MWF), a putative marker of myelination, were determined for each pathway. A positive correlation between both AL and FA and between AL and MWF were hypothesized for the three pathways. There was a selective positive correlation between AL and MWF in the right PHC (r = 0.482, p = 0.007). Thus, our results provide initial in vivo evidence for an association between myelination of the right PHC and PA in young healthy adults. Our results suggest that MWF may not only be more specific, but also more sensitive than FA to detect white matter microstructural alterations. If PA was to induce structural plasticity of the right PHC this may contribute to reverse structural alterations of the right PHC in neuropsychiatric disorder with hippocampal pathologies.

A review of white matter microstructure alterations of pathways of the reward circuit in depression.

BACKGROUND: Depressed mood, anhedonia, psychomotor retardation and alterations of circadian rhythm are core features of the depressive syndrome. Its neural correlates can be located within a frontal-striatal-tegmental neural network, commonly referred to as the reward circuit. It is the aim of this article to review literature on white matter microstructure alterations of the reward system in depression. METHOD: We searched for diffusion tensor imaging (DTI)-studies that have explored neural deficits within the cingulum bundle, the uncinate fasciculus and the supero-lateral medial forebrain bundle/anterior thalamic radiation - in adolescent and adult depression (acute and remitted), melancholic depression, treatment-resistant depression and those at familial risk of depression. The relevant diffusion MRI literature was identified using PUBMED. RESULTS: Thirty-five studies were included. In people at familial risk for depression the main finding was reduced fractional anisotropy (FA) in the cingulum bundle. Both increases and decreases of FA have been reported in the uncinate fasciculus in adolescents. Reductions of FA in the uncinate fasciculus and the anterior thalamic radiation/supero-lateral medial forebrain bundle during acute depressive episodes in adults were most consistently reported. LIMITATIONS: Non-quantitative approach. CONCLUSIONS: Altered cingulum bundle microstructure in unaffected relatives may either indicate resilience or vulnerability to depression. Uncinate fasciculus and supero-lateral medial forebrain bundle microstructure may be altered during depressive episodes in adult MDD. Future studies call for a careful clinical stratification of clinically meaningful subgroups.

Limbic white matter microstructure plasticity reflects recovery from depression.

BACKGROUND: White matter microstructure alterations of limbic and reward pathways have been reported repeatedly for depressive episodes in major depressive disorder (MDD) and bipolar disorder (BD). However, findings during remission are equivocal. It was the aim of this study to investigate if white matter microstructure changes during the time course of clinical remission. METHODS: Fifteen depressed patients (11 MDD, 4 BD) underwent diffusion-weighted MRI both during depression, and during remission following successful antidepressive treatment (average time interval between scans = 6 months). Fractional anisotropy (FA) was sampled along reconstructions of the supero-lateral medial forebrain bundle (slMFB), the cingulum bundle (CB), the uncinate fasciculus (UF), the parahippocampal cingulum (PHC) and the fornix. Repeated measures ANCOVAs controlling for the effect of age were calculated for each tract. RESULTS: There was a significant main effect of time (inter-scan interval) for mean-FA for the right CB and for the left PHC. For both pathways there was a significant time × age interaction. In the right CB, FA increased in younger patients, while FA decreased in older patients. In the left PHC, a reverse pattern was seen. FA changes in the right CB correlated positively with symptom reductions. Mean-FA of UF, slMFB and fornix did not change between the two time points. LIMITATIONS: All patients were medicated, sample size, and lack of control group. CONCLUSIONS: Right CB and left PHC undergo age-dependent plastic changes during the course of remission and may serve as a state marker in depression. UF, slMFB and FO microstructure remains stable.