White Matter Plasticity Research Articles

Goal-Oriented Attentional Self-Regulation Training in Chronic Mild Traumatic Brain Injury is Linked to Microstructural Plasticity in Prefrontal White Matter.

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.

Sex differences in patterns of white matter neuroplasticity after balance training in young adults.

In past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task. 24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training. Both females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance). The biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches).

Temporal dynamics of white and gray matter plasticity during motor skill acquisition: a comparative diffusion tensor imaging and multiparametric mapping analysis.

Learning new motor skills relies on neural plasticity within motor and limbic systems. This study uniquely combined diffusion tensor imaging and multiparametric mapping MRI to detail these neuroplasticity processes. We recruited 18 healthy male participants who underwent 960min of training on a computer-based motion game, while 14 were scanned without training. Diffusion tensor imaging, which quantifies tissue microstructure by measuring the capacity for, and directionality of, water diffusion, revealed mostly linear changes in white matter across the corticospinal-cerebellar-thalamo-hippocampal circuit. These changes related to performance and reflected different responses to upper- and lower-limb training in brain areas with known somatotopic representations. Conversely, quantitative MRI metrics, sensitive to myelination and iron content, demonstrated mostly quadratic changes in gray matter related to performance and reflecting somatotopic representations within the same brain areas. Furthermore, while myelin and iron-sensitive multiparametric mapping MRI was able to describe time lags between different cortical brain systems, diffusion tensor imaging detected time lags within the white matter of the motor systems. These findings suggest that motor skill learning involves distinct phases of white and gray matter plasticity across the sensorimotor network, with the unique combination of diffusion tensor imaging and multiparametric mapping MRI providing complementary insights into the underlying neuroplastic responses.

White matter microstructural plasticity associated with educational intervention in reading disability.

Children's reading progress typically slows during extended breaks in formal education, such as summer vacations. This stagnation can be especially concerning for children with reading difficulties or disabilities, such as dyslexia, because of the potential to exacerbate the skills gap between them and their peers. Reading interventions can prevent skill loss and even lead to appreciable gains in reading ability during the summer. Longitudinal studies relating intervention response to brain changes can reveal educationally relevant insights into rapid learning-driven brain plasticity. The current work focused on reading outcomes and white matter connections, which enable communication among the brain regions required for proficient reading. We collected reading scores and diffusion-weighted images at the beginning and end of summer for 41 children with reading difficulties who had completed either 1st or 2nd grade. Children were randomly assigned to either receive an intensive reading intervention (n = 26; Seeing Stars from Lindamood-Bell which emphasizes orthographic fluency) or be deferred to a wait-list group (n = 15), enabling us to analyze how white matter properties varied across a wide spectrum of skill development and regression trajectories. On average, the intervention group had larger gains in reading compared to the non-intervention group, who declined in reading scores. Improvements on a proximal measure of orthographic processing (but not other more distal reading measures) were associated with decreases in mean diffusivity within core reading brain circuitry (left arcuate fasciculus and left inferior longitudinal fasciculus) and increases in fractional anisotropy in the left corticospinal tract. Our findings suggest that responses to intensive reading instruction are related predominantly to white matter plasticity in tracts most associated with reading.

White Matter Plasticity Underpins Cognitive Gains After Multidomain Adaptive Computerized Cognitive Training.

This study aims to evaluate the effectiveness of computerized cognitive training (CCT) on white matter (WM) neuroplasticity and neuropsychological performance. A total of 128 community older adults (64.36 ± 6.14 years) were recruited and randomly assigned to the intervention or control group. Participants in the intervention group received a home-based, multidomain, and adaptive CCT for 30 minutes, 2 days per week for 1 year. Neuropsychological assessments, diffusion magnetic resonance imaging (MRI), and T1-weighted structural MRI were performed at the pre- and post-intervention visits. Eighty-one of 128 participants (41 in the intervention group and 40 in the control group) completed the 1-year intervention, and 61 of them (27 in the intervention group and 34 in the control group) underwent MRI scans twice. After excluding attrition bias, a significant time-by-group interaction on the Stroop Color-Word Test (SCWT; F = 51.85, p < .001) was found, showing improvement in the intervention group and a decline in the control group. At the brain level, the intervention group exhibited increased axial diffusivity in the left posterior thalamic radiation, and this increase was significantly correlated with reduced SCWT reaction time (r = ‒0.42, p = .029). No significant time-by-group interactions were found for gray matter volume. Our findings suggest that conducting multidomain adaptive CCT is an effective and feasible method to counteract cognitive decline in older adults, with WM neuroplasticity underpinning cognitive improvements. This study contributes to the understanding of the neural basis for the beneficial effect of CCT for older adults.

White matter plasticity during second language learning within and across hemispheres

Adult second language (L2) learning is a challenging enterprise inducing neuroplastic changes in the human brain. However, it remains unclear how the structural language connectome and its subnetworks change during adult L2 learning. The current study investigated longitudinal changes in white matter (WM) language networks in each hemisphere, as well as their interconnection, in a large group of Arabic-speaking adults who learned German intensively for 6 mo. We found a significant increase in WM-connectivity within bilateral temporal-parietal semantic and phonological subnetworks and right temporal-frontal pathways mainly in the second half of the learning period. At the same time, WM-connectivity between the two hemispheres decreased significantly. Crucially, these changes in WM-connectivity are correlated with L2 performance. The observed changes in subnetworks of the two hemispheres suggest a network reconfiguration due to lexical learning. The reduced interhemispheric connectivity may indicate a key role of the corpus callosum in L2 learning by reducing the inhibition of the language-dominant left hemisphere. Our study highlights the dynamic changes within and across hemispheres in adult language-related networks driven by L2 learning.

Modifiers of Individual Differences and Within‐person Changes in the Aging White Matter

AbstractMy talk will focus on: 1) longitudinal changes and plasticity, and 2) lifestyle and health modifiers of white matter (WM) health in aging.First, individual differences in changes in WM microstructure may be key for identifying preclinical stages of dementia, opening new opportunities for early interventions. I will present the outcomes from a meta‐analysis and systematic review (Colmenares et al., in preparation) based on 28 diffusion tensor imaging (DTI) studies in healthy adults from the past 10 years, addressing the following questions: Over what time periods can decline in WM microstructure be detected using MRI? Do within‐person changes accelerate with age and vary by brain region? What are the modifiers of within‐person changes in WM? Also, for decades, adult WM has been perceived as a “passive” (i.e., only relaying electrical signals) and “static” (i.e., not capable of or involved in neuroplasticity). Despite emerging evidence in rodents on short‐term structural WM changes, evidence for such experience‐induced plasticity in adult humans remains inconclusive. Thus, I summarize evidence from clinical studies to discuss whether the adult WM microstructure is malleable with experience, and what interventions may be the most promising in inducing a change. I will also present our findings on exercise‐induced WM plasticity in older age, using DTI and T1/T2 ratio imaging (Colmenares et al., 2021, Burzynska et al., 2017).Second, lack of physical activity (PA) and sedentary lifestyles are independently associated with increased risk of metabolic and cardiovascular diseases, mortality, and ADRD. Regular PA decreases inflammation and improves vascular function and perfusion. In contrast, insufficient PA and/or excessive sedentary behaviors is known to upregulate markers of metabolic stress and inflammation. I will briefly review our past work relating sensor‐measured PA with WM health, measured with DTI. Then, I will present our ongoing work using quantitative MRI, such as Myelin Water Imaging and Neurite Orientation Dispersion and Density Imaging. For example, I will present associations between systemic health (i.e., BMI, waist circumference, blood pressure, blood glucose and cholesterol), sensor‐measured physical activity (i.e., time spend sedentary and in light, moderate or vigorous physical activity), and myelin and axonal content in healthy adults.

Acceptance and Commitment Therapy and white matter plasticity in individuals with subclinical depression and psychotic experiences: A Randomised Controlled Trial

BackgroundResearch indicates that Acceptance and Commitment Therapy in Daily Life (ACT-DL) is effective in reducing symptoms of depression, anxiety and psychosis. During adolescence, vulnerability to psychopathology peaks, creating a window for early interventions, while white matter development is ongoing. This study aims to examine microstructural white matter after ACT-DL intervention in youngsters with mild psychopathology. MethodsForty-five individuals with mild psychopathology were randomly allocated to ACT-DL (n=20) or topic discussion control (TD, n=25). Symptomatology was assessed with the Community Assessment of Psychic Experiences (CAPE), Montgomery–Åsberg Depression Rating Scale (MADRS) and the Experience Sampling Method (ESM). Diffusion Weighted Imaging (DWI) and network-connectivity parameters were obtained and compared before and after the intervention/control condition. Interactions between microstructural white matter change and condition were examined in models of CAPE positive symptoms and ESM subclinical psychotic experiences (PE) and negative affect (NA) levels. ResultsACT-DL, compared to TD, was associated with changes on subclinical depressive and psychotic symptom levels. There was no significant change in DWI or network connectivity in either condition and no significant difference between both conditions. In the model of NA, several regional interactions between condition and network measures were significant, but stratification per condition provided no significant associations. There were no significant interactions between DWI or network connectivity parameters and condition in the models of the CAPE positive symptoms, MADRS and PE. ConclusionsThe findings suggest that behavioral (symptom) changes are more sensitive to a five-week psychological training than microstructural white matter changes which did not show significant changes over time.

Myelin plasticity during early literacy training in at-risk pre-readers

A growing body of neuroimaging evidence shows that white matter can change as a result of experience and structured learning. Although the majority of previous work has used diffusion MRI to characterize such changes in white matter, diffusion metrics offer limited biological specificity about which microstructural features may be driving white matter plasticity. Recent advances in myelin-specific MRI techniques offer a promising opportunity to assess the specific contribution of myelin in learning-related plasticity. Here we describe the application of such an approach to examine structural plasticity during an early intervention in preliterate children at risk for dyslexia. To this end, myelin water imaging data were collected before and after a 12-week period in (1) at-risk children following early literacy training (n = 13–24), (2) at-risk children engaging with other non-literacy games (n = 10–17) and (3) children without a risk receiving no training (n = 11–22). Before the training, regional risk-related differences were identified, showing higher myelin water fraction (MWF) in right dorsal white matter in at-risk children compared to the typical control group. Concerning intervention-specific effects, our results revealed an increase across left-hemispheric and right ventral MWF over the course of training in the at-risk children receiving early literacy training, but not in the at-risk active control group or the no-risk typical control group. Overall, our results provide support for the use of myelin water imaging as a sensitive tool to investigate white matter and offer a first indication of myelin plasticity in young children at the onset of literacy acquisition.

Introducing the Neuroplastic Narrative: a non-pathologizing biological foundation for trauma-informed and adverse childhood experience aware approaches.

Most people accessing mental health services have adverse childhood experiences (ACEs) and/or histories of complex trauma. In recognition of this, there are calls to move away from medical model approaches and move toward trauma-informed approaches which privilege the impact of life experience over underlying pathology in the etiology of emotional and psychological suffering. Trauma-informed approaches lack a biological narrative linking trauma and adversity to later suffering. In its absence, this suffering is diagnosed and treated as a mental illness. This study articulates the Neuroplastic Narrative, a neuroecological theory that fills this gap, conceptualizing emotional and psychological suffering as the cost of surviving and adapting to the impinging environments of trauma and adversity. The Neuroplastic Narrative privileges lived experience and recognizes that our experiences become embedded in our biology through evolved mechanisms that ultimately act to preserve survival in the service of reproduction. Neuroplasticity refers to the capacity of neural systems to adapt and change. Our many evolved neuroplastic mechanisms including epigenetics, neurogenesis, synaptic plasticity, and white matter plasticity allow us to learn from, and adapt to, past experiences. This learning and adaption in turn allows us to better anticipate and physiologically prepare for future experiences that (nature assumes) are likely to occur, based on past experiences. However, neuroplastic mechanisms cannot discriminate between experiences; they function to embed experience regardless of the quality of that experience, generating vicious or virtuous cycles of psychobiological anticipation, to help us survive or thrive in futures that resemble our privileged or traumatic pasts. The etiology of suffering that arises from this process is not a pathology (a healthy brain is a brain that can adapt to experience) but is the evolutionary cost of surviving traumatizing environments. Misidentifying this suffering as a pathology and responding with diagnosis and medication is not trauma-informed and may cause iatrogenic harm, in part through perpetuating stigma and exacerbating the shame which attends complex trauma and ACEs. As an alternative, this study introduces the Neuroplastic Narrative, which is situated within an evolutionary framework. The Neuroplastic Narrative complements both Life History and Attachment Theory and provides a non-pathologizing, biological foundation for trauma-informed and Adverse Childhood Experience aware approaches.

Evidence of lateralised white matter plasticity: A longitudinal study of balance performance in nonexpert healthy adults.

Training-induced plasticity by practicing expert skills has been of particular interest; however, little is known about white matter plasticity for improving a fundamental element of body function, such as balance or postural control. This study explored white matter plasticity in nonexpert healthy adults, based on stepwise balance training. Seventeen participants were included and performed a home-based balance training program for 4weeks (30 min/day, 3days/week). Before commencing training, they underwent a baseline diffusion tensor imaging scan. A second scan was acquired at the end of the 4-week training. Lateralised balance load was applied on the right leg to contrast any lateralised effect on the white matter tracts. The balance function was assessed using the Community Balance & Mobility Scale. We examined changes in the fractional anisotropy values of the tracts of interest between pre- and post-training. After the 4-week training, the fractional anisotropy values were enhanced in the right superior cerebellar peduncle, transverse pontine fibre, body of the corpus callosum, left fornix and left uncinate fasciculus. The Community Balance & Mobility Scalescore improved after 4-week training, but an association with changes in fractional anisotropy values cannot be evaluated due to the ceiling effect of the balance assessment tools. Balance training can strengthen the cerebro-cerebellar and interhemispheric structural connections and induce microstructural changes in the limbic structures, including the fornix and uncinate fasciculus. The effect of a lateralised balance load could be projected to the specific white matter tracts in a lateralised manner.

White Matter Changes after Neurobehavioral Therapy for Functional Seizures.

We aimed to prospectively quantify changes in white matter morphology after neurobehavioral therapy (NBT) for functional seizures (FS) using neurite orientation dispersion and density imaging (NODDI). We hypothesized that patients with FS would exhibit white matter plasticity in the uncinate fasciculus, fornix/stria terminalis, cingulum, and corticospinal tract following NBT that would correlate with improvements in affective symptoms, postconcussive symptoms, and quality of life (QOL). Forty-two patients with traumatic brain injury (TBI) and FS (TBI+FS) underwent NBT and provided pre-/postintervention neuroimaging and behavioral data; 47 controls with TBI without FS (TBI-only) completed the same measures but did not receive NBT. Changes in neurite density, orientation dispersion (orientation dispersion index [ODI]), and extracellular free water (FW) were compared between groups. Significant ODI increases in the left uncinate fasciculus in TBI+FS (mean difference = 0.017, p = 0.039) correlated with improvements in posttraumatic symptoms (r = -0.395, p = 0.013), QOL (r = 0.474, p = 0.002), emotional well-being (r = 0.524, p < 0.001), and energy (r = 0.474, p = 0.002). In TBI-only, ODI decreased (mean difference = -0.008, p = 0.047) and FW increased (mean difference = 0.011, p = 0.003) in the right cingulum. FW increases correlated with increased psychological problems (r = 0.383, p = 0.013). In TBI+FS, NBT resulted in FS decreases of 3.5 seizures per week. None of the imaging changes correlated with FS frequency. We identified white matter changes after NBT in patients with FS that were associated with improved psychosocial functioning. NODDI could be incorporated into future mechanistic assessments of interventions in patients with FS. ANN NEUROL 2023;94:350-365.

White matter plasticity following cataract surgery in congenitally blind patients

The visual system develops abnormally when visual input is absent or degraded during a critical period early in life. Restoration of the visual input later in life is generally thought to have limited benefit because the visual system will lack sufficient plasticity to adapt to and utilize the information from the eyes. Recent evidence, however, shows that congenitally blind adolescents can recover both low-level and higher-level visual function following surgery. In this study, we assessed behavioral performance in both a visual acuity and a face perception task alongside longitudinal structural white matter changes in terms of fractional anisotropy (FA) and mean diffusivity (MD). We studied congenitally blind patients with dense bilateral cataracts, who received cataract surgery at different stages of adolescence. Our goal was to differentiate between age- and surgery-related changes in both behavioral performance and structural measures to identify neural correlates which might contribute to recovery of visual function. We observed surgery-related long-term increases of structural integrity of late-visual pathways connecting the occipital regions with ipsilateral fronto-parieto-temporal regions or homotopic contralateral areas. Comparison to a group of age-matched healthy participants indicated that these improvements went beyond the expected changes in FA and MD based on maturation alone. Finally, we found that the extent of behavioral improvement in face perception was mediated by changes in structural integrity in late visual pathways. Our results suggest that sufficient plasticity remains in adolescence to partially overcome abnormal visual development and help localize the sites of neural change underlying sight recovery.

Coherent, time-shifted patterns of microstructural plasticity during motor-skill learning

Motor skill learning relies on neural plasticity in the motor and limbic systems. However, the spatial and temporal characteristics of these changes—and their microstructural underpinnings—remain unclear. Eighteen healthy males received 1 h of training in a computer-based motion game, 4 times a week, for 4 consecutive weeks, while 14 untrained participants underwent scanning only. Performance improvements were observed in all trained participants. Serial myelin- and iron-sensitive multiparametric mapping at 3T during this period of intensive motor skill acquisition revealed temporally and spatially distributed, performance-related microstructural changes in the grey and white matter across a corticospinal-cerebellar-hippocampal circuit. Analysis of the trajectory of these transient changes suggested time-shifted cascades of plasticity from the dominant sensorimotor system to the contralateral hippocampus. In the cranial corticospinal tracts, changes in myelin-sensitive metrics during training in the posterior limb of the internal capsule were of greater magnitude in those who trained their upper limbs vs. lower limb trainees. Motor skill learning is associated with waves of grey and white matter plasticity, across a broad sensorimotor network.

Cortical stimulation leads to shortened myelin sheaths and increased axonal branching in spared axons after cervical spinal cord injury.

Neural activity and learning lead to myelin sheath plasticity in the intact central nervous system (CNS), but this plasticity has not been well-studied after CNS injury. In the context of spinal cord injury (SCI), demyelination occurs at the lesion site and natural remyelination of surviving axons can take months. To determine if neural activity modulates myelin and axon plasticity in the injured, adult CNS, we electrically stimulated the contralesional motor cortex at 10 Hz to drive neural activity in the corticospinal tract of rats with sub-chronic spinal contusion injuries. We quantified myelin and axonal characteristics by tracing corticospinal axons rostral to and at the lesion epicenter and identifying nodes of Ranvier by immunohistochemistry. Three weeks of daily stimulation induced very short myelin sheaths, axon branching, and thinner axons outside of the lesion zone, where remodeling has not previously been reported. Surprisingly, remodeling was particularly robust rostral to the injury which suggests that electrical stimulation can promote white matter plasticity even in areas not directly demyelinated by the contusion. Stimulation did not alter myelin or axons at the lesion site, which suggests that neuronal activity does not contribute to myelin remodeling near the injury in the sub-chronic period. These data are the first to demonstrate wide-scale remodeling of nodal and myelin structures of a mature, long-tract motor pathway in response to electrical stimulation. This finding suggests that neuromodulation promotes white matter plasticity in intact regions of pathways after injury and raises intriguing questions regarding the interplay between axonal and myelin plasticity.

Nuancing the Limitations of Axonal Plasticity in World Health Organization Grade II Gliomas: White Matter Tracts Compensation Is Driven by Cortical Remodeling.

Diffuse World Health Organization grade II glioma (GIIG) is a slow-growing brain cancer that migrates along the white matter (WM) tracts. Neuroplastic changes were described in reaction to GIIG progression, opening the window to extensive cerebral surgical resection in patients able to resume an active life with no functional consequences. However, atlases of cortico-subcortical neural plasticity emphasized the limited potential of axonal reorganization. Yet, the removal of WM involved by GIIG can be possible, at least to some extent, without generating permanent neurological disturbances. Here, the aim was to discuss mechanisms underlying functional compensation which make feasible resection of the subcortical component of GIIG and to propose a new model of adaptative neural reconfiguration at the level of the axonal connectivity. In this model, 2 parts of the WM tracts are considered: (1) the stem of the bundle that represents the actual limitation of plastic potential, as supported by reproducible behavioral disorders elicited by intraoperative axonal electrostimulation mapping (ESM) and (2) the terminations/origins of the bundle that may no longer be critical in case of functional reallocation of the cortex to/from which these WM fibers run-thus inducing no behavioral troubles during direct ESM. Understanding that a certain degree of axonal compensation in specific portions of the tracts is driven by cortical remodeling may enable to rethink the concept of WM plasticity and to refine the preoperative estimation of extent of resection for GIIG. Identifying eloquent fibers by ESM, especially their convergence in the depth, is essential to achieve an individualized connectome-based resection.

Possible Effects of Acupuncture in Poststroke Aphasia.

Neural plasticity promotes the reorganization of language networks and is an essential recovery mechanism for poststroke aphasia (PSA). Neuroplasticity may be a pivotal bridge to elucidate the potential recovery mechanisms of acupuncture for aphasia. Therefore, understanding the neuroplasticity mechanism of acupuncture in PSA is crucial. However, the underlying therapeutic mechanism of neuroplasticity in PSA after acupuncture needs to be explored. Excitotoxicity after brain injury affects the activity of neurotransmitters and disrupts the transmission of normal neuron information. Thus, a helpful strategy of acupuncture might be to improve PSA by affecting the availability of these neurotransmitters and glutamate receptors at synapses. In addition, the regulation of neuroplasticity by acupuncture may also be related to the regulation of astrocytes. Considering the guiding significance of acupuncture for clinical treatment, it is necessary to carry out further study about the influence of acupuncture on the recovery of aphasia after stroke. This study summarizes the current research on the neural mechanism of acupuncture in treating PSA. It seeks to elucidate the potential effect of acupuncture on the recovery of PSA from the perspective of synaptic plasticity and integrity of gray and white matter.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Lack of effects of four-week theta burst stimulation on white matter macro/microstructure in children and adolescents with autism

Following the published behavioral and cognitive results of this single-blind parallel sham-controlled randomized clinical trial, the current study aimed to explore the impact of intermittent theta burst stimulation (iTBS), a variant of excitatory transcranial magnetic stimulation, over the bilateral posterior superior temporal sulci (pSTS) on white matter macro/microstructure in intellectually able children and adolescents with autism. Participants were randomized and blindly received active or sham iTBS for 4 weeks (the single-blind sham-controlled phase). Then, all participants continued to receive active iTBS for another 4 weeks (the open-label phase). The clinical results were published elsewhere. Here, we present diffusion magnetic resonance imaging data on potential changes in white matter measures after iTBS. Twenty-two participants in Active-Active group and 27 participants in Sham-Active group underwent multi-shell high angular resolution diffusion imaging (64-direction for b = 2000 & 1000 s/mm2, respectively) at baseline, week 4, and week 8. With longitudinal fixel-based analysis, we found no white matter changes following iTBS from baseline to week 4 (a null treatment by time interaction and a null within-group paired comparison in the Active-Active group), nor from baseline to week 8 (null within-group paired comparisons in both Active-Active and Sham-Active groups). As for the brain-symptoms relationship, we did not find baseline white matter metrics associated with symptom changes at week 4 in either group. Our results raise the question of what the minimal cumulative stimulation dose required to induce the white matter plasticity is.

White matter brain structure predicts language performance and learning success.

Individual differences in the ability to process language have long been discussed. Much of the neural basis of these, however, is yet unknown. Here we investigated the relationship between long-range white matter connectivity of the brain, as revealed by diffusion tractography, and the ability to process syntactically complex sentences in the participants' native language as well as the improvement thereof by multiday training. We identified specific network motifs by singular value decomposition that indeed related white matter structural connectivity to individual language processing performance. First, for two such motifs, one in the left and one in the right hemisphere, their individual prevalence significantly predicted the individual language performance, suggesting an anatomical predisposition for the individual ability to process syntactically complex sentences. Both motifs comprise a number of cortical regions, but seem to be dominated by areas known for the involvement in working memory rather than the classical language network itself. Second, we identified another left hemispheric network motif, whose change of prevalence over the training period significantly correlated with the individual change in performance, thus reflecting training induced white matter plasticity. This motif comprises diverse cortical areas including regions known for their involvement in language processing, working memory and motor functions. The present findings suggest that individual differences in language processing and learning can be explained, in part, by individual differences in the brain's white matter structure. Brain structure may be a crucial factor to be considered when discussing variations in human cognitive performance, more generally.