Impaired sleep-dependent memory consolidation predicted by reduced sleep spindles in Rolandic epilepsy.

Background and Objectives: Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy. Methods: In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector. Results: Twenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute). Discussion: Children with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.

Decreased thalamocortical connectivity in resolved Rolandic epilepsy.

OBJECTIVE: Median nerve somatosensory evoked fields (SEFs) conduction times reflect the integrity of neural transmission across the thalamocortical circuit. We hypothesized median nerve SEF conduction time would be abnormal in children with Rolandic epilepsy (RE). METHODS: 22 children with RE (10 active; 12 resolved) and 13 age-matched controls underwent structural and diffusion MRI and median nerve and visual stimulation during magnetoencephalography (MEG). N20 SEF responses were identified in contralateral somatosensory cortices. P100 were identified in contralateral occipital cortices as controls. Conduction times were compared between groups in linear models controlling for height. N20 conduction time was also compared to thalamic volume and Rolandic thalamocortical structural connectivity inferred using probabilistic tractography. RESULTS: The RE group had slower N20 conduction compared to controls (p = 0.042, effect size 0.6 ms) and this difference was driven by the resolved RE group (p = 0.046). There was no difference in P100 conduction time between groups (p = 0.83). Ventral thalamic volume positively correlated with N20 conduction time (p = 0.014). CONCLUSIONS: Children with resolved RE have focally decreased Rolandic thalamocortical connectivity. SIGNIFICANCE: These results identify a persistent focal thalamocortical circuit abnormality in resolved RE and suggest that decreased Rolandic thalamocortical connectivity may support symptom resolution in this self-limited epilepsy.

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy.

OBJECTIVE: Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non-rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high-dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE-SWAS: (1) spikes and spindles would be anti-correlated, (2) high-dose diazepam would increase spindles and decrease spikes, and (3) spindle response would be greater in those with cognitive improvement. METHODS: Consecutive EE-SWAS patients treated with high-dose diazepam that met the criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre- and post-treatment NREM sleep. Spikes were quantified using a validated automated spike detector. The cognitive response was determined from a chart review. RESULTS: Spindle rate was anti-correlated with the spike rate in the channel with the maximal spike rate (p = 0.002) and averaged across all channels (p = 0.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high-dose diazepam treatment (p ≤ 2e-5, all tests). Spindle rate, duration, and percentage (p ≤ 0.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spindle rate but not changes in spike rate distinguished between groups. INTERPRETATION: These findings confirm thalamocortical disruption in EE-SWAS, identify a mechanism through which benzodiazepines may support cognitive recovery, and introduce sleep spindles as a promising mechanistic biomarker to detect treatment response in severe epileptic encephalopathies.

Preliminary evidence of a relationship between sleep spindles and treatment response in epileptic encephalopathy.

Objective: Epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non-rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high-dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE-SWAS: 1) spikes and spindles would be anticorrelated, 2) high-dose diazepam would increase spindles and decrease spikes, and 3) spindle response would be greater in those with cognitive improvement. Methods: Consecutive EE-SWAS patients treated with high-dose diazepam that met criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre- and post-treatment NREM sleep. Spikes were quantified using a validated automated spike detector. Cognitive response was determined from chart review. Results: Spindle rate was anticorrelated with spike rate in the channel with the maximal spike rate ( p =0.002) and averaged across all channels ( p =0.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high-dose diazepam treatment ( p≤ 2e-5, all tests). Spindle rate, duration, and percentage ( p ≤0.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spike rate did not distinguish between groups. Interpretation: These findings confirm thalamocortical disruption in EE-SWAS, identify a mechanism through which benzodiazepines may support cognitive recovery, and introduce sleep spindles as a promising mechanistic biomarker to detect treatment response in severe epileptic encephalopathies.

Sleep spindles in the healthy brain from birth through 18 years.

STUDY OBJECTIVE: Sleep spindles are present from birth and reflect cognitive functions across the lifespan, but normative values for this cognitive biomarker across development are lacking. This study aims to establish normative spindle features over development. METHODS: All available normal 19-channel electroencephalograms from developmentally normal children between February 2002 and June 2021 in the MGH EEG lab were analyzed. Approximately, 20 000 spindles were hand-marked to train and validate an automated spindle detector across ages. Normative values for spindle rate, duration, frequency, refractory period, and interhemispheric lag are provided for each channel and each age. RESULTS: Sleep EEGs from 567 developmentally normal children (range 0 days to 18 years) were included. The detector had excellent performance (F1 = 0.47). Maximal spindle activity is seen over central regions during infancy and adolescence and frontopolar regions during childhood. Spindle rate and duration increase nonlinearly, with the most rapid changes during the first 4 months of life and between ages 3 and 14 years. Peak spindle frequency follows a U-shaped curve and discrete frontal slow and central fast spindles are evident by 18 months. Spindle refractory periods decrease between ages 1 and 14 years while interhemispheric asynchrony decreases over the first 3 months of life and between ages 1 and 14 years. CONCLUSIONS: These data provide age- and region-specific normative values for sleep spindles across development, where measures that deviate from these values can be considered pathological. As spindles provide a noninvasive biomarker for cognitive function across the lifespan, these normative measures can accelerate the discovery and diagnosis in neurodevelopmental disorders.

Early neural activity changes associated with stimulus detection during visual conscious perception.

The earliest cortical neural signals following consciously perceived visual stimuli in humans are poorly understood. Using intracranial electroencephalography, we investigated neural activity changes associated with the earliest stages of stimulus detection during visual conscious perception. Participants (N = 10; 1,693 electrode contacts) completed a continuous performance task where subjects were asked to press a button when they saw a target letter among a series of nontargets. Broadband gamma power (40-115 Hz) was analyzed as marker of cortical population neural activity. Regardless of target or nontarget letter type, we observed early gamma power changes within 30-180 ms from stimulus onset in a network including increases in bilateral occipital, fusiform, frontal (including frontal eye fields), and medial temporal cortex; increases in left lateral parietal-temporal cortex; and decreases in the right anterior medial occipital cortex. No significant differences were observed between target and nontarget stimuli until >180 ms post-stimulus, when we saw greater gamma power increases in left motor and premotor areas, suggesting a possible role in perceptual decision-making and/or motor responses with the right hand. The early gamma power findings support a broadly distributed cortical visual detection network that is engaged at early times tens of milliseconds after signal transduction from the retina.

Human visual consciousness involves large scale cortical and subcortical networks independent of task report and eye movement activity.

The full neural circuits of conscious perception remain unknown. Using a visual perception task, we directly recorded a subcortical thalamic awareness potential (TAP). We also developed a unique paradigm to classify perceived versus not perceived stimuli using eye measurements to remove confounding signals related to reporting on conscious experiences. Using fMRI, we discovered three major brain networks driving conscious visual perception independent of report: first, increases in signal detection regions in visual, fusiform cortex, and frontal eye fields; and in arousal/salience networks involving midbrain, thalamus, nucleus accumbens, anterior cingulate, and anterior insula; second, increases in frontoparietal attention and executive control networks and in the cerebellum; finally, decreases in the default mode network. These results were largely maintained after excluding eye movement-based fMRI changes. Our findings provide evidence that the neurophysiology of consciousness is complex even without overt report, involving multiple cortical and subcortical networks overlapping in space and time.

Transient, developmental functional and structural connectivity abnormalities in the thalamocortical motor network in Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common focal, idiopathic, developmental epilepsy, characterized by a transient period of sleep-potentiated seizures and epileptiform discharges in the inferior Rolandic cortex during childhood. The cause of RE remains unknown but converging evidence has identified abnormalities in the Rolandic thalamocortical circuit. To better localize this transient disease, we evaluated Rolandic thalamocortical functional and structural connectivity in the sensory and motor circuits separately during the symptomatic and asymptomatic phases of this disease. We collected high resolution structural, diffusion, and resting state functional MRI data in a prospective cohort of children with active RE (n = 17), resolved RE (n = 21), and controls (n = 33). We then computed the functional and structural connectivity between the inferior Rolandic cortex and the ventrolateral (VL) nucleus of the thalamus (efferent pathway) and the ventroposterolateral (VPL) nucleus of the thalamus (afferent pathway) across development in children with active, resolved RE and controls. We compared connectivity with age in each group using linear mixed-effects models. We found that children with active RE have increasing thalamocortical functional connectivity between the VL thalamus and inferior motor cortex with age (p = 0.022) that is not observed in controls or resolved RE. In contrast, children with resolved RE have increasing thalamocortical structural connectivity between the VL nucleus and the inferior motor cortex with age (p = 0.025) that is not observed in controls or active RE. No relationships were identified between VPL nuclei and the inferior sensory cortex with age in any group. These findings localize the functional and structural thalamocortical circuit disruption in RE to the efferent thalamocortical motor pathway. Further work is required to determine how these circuit abnormalities contribute to the emergence and resolution of symptoms in this developmental disease.

Early cortical signals in visual stimulus detection.

During visual conscious perception, the earliest responses linked to signal detection are little known. The current study aims to reveal the cortical neural activity changes in the earliest stages of conscious perception using recordings from intracranial electrodes. Epilepsy patients (N=158) were recruited from a multi-center collaboration and completed a visual word recall task. Broadband gamma activity (40-115Hz) was extracted with a band-pass filter and gamma power was calculated across subjects on a common brain surface. Our results show early gamma power increases within 0-50ms after stimulus onset in bilateral visual processing cortex, right frontal cortex (frontal eye fields, ventral medial/frontopolar, orbital frontal) and bilateral medial temporal cortex regardless of whether the word was later recalled. At the same early times, decreases were seen in the left rostral middle frontal gyrus. At later times after stimulus onset, gamma power changes developed in multiple cortical regions. These included sustained changes in visual and other association cortical networks, and transient decreases in the default mode network most prominently at 300-650ms. In agreement with prior work in this verbal memory task, we also saw greater increases in visual and medial temporal regions as well as prominent later (> 300ms) increases in left hemisphere language areas for recalled versus not recalled stimuli. These results suggest an early signal detection network in the frontal, medial temporal, and visual cortex is engaged at the earliest stages of conscious visual perception.

White Matter Integrity Is Associated With the Amount of Physical Activity in Older Adults With Super-aging.

Previous studies have introduced the concept of "SuperAgers," defined as older adults with youthful memory performance associated with the increased cortical thickness of the anterior cingulate cortex. Given that age-related structural brain changes are observed earlier in the white matter (WM) than in the cortical areas, we investigated whether WM integrity is different between the SuperAgers (SA) and typical agers (TA) and whether it is associated with superior memory performance as well as a healthy lifestyle. A total of 35 SA and 55 TA were recruited for this study. Further, 3.0-T magnetic resonance imaging (MRI), neuropsychological tests, and lifestyle factors related to cognitive function, such as physical activity and duration of sleep, were evaluated in all participants. SA was defined as individuals demonstrating the youthful performance of verbal and visual memory, as measured by the Seoul Verbal Learning Test (SVLT) and the Rey-Osterrieth Complex Figure Test (RCFT), respectively. Tract-based spatial statistics (TBSS) analysis was used to compare the diffusion values such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) between the SA and TA. SA exhibited better performance in memory, attention, visuospatial, and frontal executive functions than the TA did. SA also exhibited greater amounts of physical activity than the TA did. As compared to TA, SA demonstrated higher FA with lower MD, RD, and AD in the corpus callosum and higher FA and lower RD in the right superior longitudinal fasciculus (SLF), which is significantly associated with memory function. Interestingly, FA values of the body of corpus callosum were correlated with the amount of physical activity. Our findings suggest that WM integrity of the corpus callosum is associated with superior memory function and a higher level of physical activities in SA compared to TA.

Urate is closely linked to white matter integrity in multiple system atrophy.

OBJECTIVE: We aimed to investigate the association of the serum urate level with cortical thickness and white matter integrity in multiple system atrophy (MSA). METHODS: We recruited 75 MSA patients and 42 controls who underwent brain MRI and measured serum urate level at baseline. Using cortical thickness and tract-based spatial statistics analyses, we investigated the correlation between serum urate levels and cortical thickness or diffusion tensor imaging (DTI) measures in controls and MSA patients. Interaction effects were analyzed to find different patterns of correlation according to sex and clinical subtype. We evaluated the relationship between serum urate levels, DTI measures, and total UMSARS score, using path analysis. RESULTS: Serum urate levels showed a positive correlation with FA values in the corpus callosum and a negative correlation with MD values in widespread regions including cerebellar, brainstem, and cerebral white matter in patients with MSA. Both sexes showed a negative correlation between serum urate levels and MD values without significant interaction effect. In subgroup analysis according to subtype, patients with cerebellar subtype showed a negative correlation. Serum urate levels did not correlated with cortical thickness. Path analysis showed that MD values in middle and inferior cerebellar peduncle mediated the association between serum urate level and total UMSAR score. INTERPRETATION: The present study demonstrated that serum urate levels played a pivotal role in white matter disintegrity and clinical disability in MSA. It would provide an evidence of the role of urate as a potential neuroprotective factor against white matter neurodegeneration in MSA.

Author Correction: Multimodal imaging analyses in patients with genetic and sporadic forms of small vessel disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Default mode and visual network activity in an attention task: Direct measurement with intracranial EEG.

Dynamic attention states are necessary to navigate the ever changing task demands of daily life. Previous investigations commonly utilize a block paradigm to study sustained and transient changes in attention networks. fMRI investigations have shown that sustained attention in visual block design attention tasks corresponds to decreased signal in the default mode and visual processing networks. While task negative networks are anticipated to decrease during active task engagement, it is unexpected that visual networks would also be suppressed during a visual task where event-related fMRI studies have found transient increases to visual stimuli. To resolve these competing results, the current investigations utilized intracranial EEG to directly interrogate visual and default mode network dynamics during a visual continuous performance task. We used the electrophysiological data to model expected fMRI signals and to maximize interpretation of current results with previous investigations. Results show broadband gamma power decreases in the default mode network, corresponding to previous EEG and fMRI findings. Meanwhile, visual processing regions including the primary visual cortex and fusiform gyrus demonstrate both sustained decreases during task engagement and stimuli-driven transient increases in gamma power. Modeled fMRI based on gamma power reproduces signal decreases reported in the fMRI literature, and emphasizes the insensitivity of fMRI to transient, regularly spaced signal changes embedded within sustained network dynamics. The signal processing functions of the dynamic visual and default mode network changes explored in this study are unknown but may be elucidated through further investigation.

Frontal atrophy as a marker for dementia conversion in Parkinson's disease with mild cognitive impairment.

This study aimed to investigate the cortical neural correlates of dementia conversion in Parkinson's disease with mild cognitive impairment (PD-MCI). We classified 112 patients with drug-naïve early stage PD meeting criteria for PD-MCI into either PD with dementia (PDD) converters (n = 34) or nonconverters (n = 78), depending on whether they developed dementia within 4 years of PD diagnosis. Cortical thickness analyses were performed in 34 PDD converters and 34 matched nonconverters. Additionally, a linear discriminant analysis was performed to distinguish PDD converters from nonconverters using cortical thickness of the regions that differed between the two groups. The PDD converters had higher frequencies of multiple domain MCI and amnestic MCI with storage failure, and poorer cognitive performances on frontal/executive, memory, and language function domains than did the nonconverters. Cortical thinning extending from the posterior cortical area into the frontal region was observed in PDD converters relative to nonconverters. The discriminant analysis showed that the prediction model with two cortical thickness variables in the right medial superior frontal and left olfactory cortices optimally distinguished PDD converters from nonconverters. Our data suggest that cortical thinning in the frontal areas including the olfactory cortex is a marker for early dementia conversion in PD-MCI.

A Physarum Centrality Measure of the Human Brain Network.

The most important goals of brain network analyses are to (a) detect pivotal regions and connections that contribute to disproportionate communication flow, (b) integrate global information, and (c) increase the brain network efficiency. Most centrality measures assume that information propagates in networks with the shortest connection paths, but this assumption is not true for most real networks given that information in the brain propagates through all possible paths. This study presents a methodological pipeline for identifying influential nodes and edges in human brain networks based on the self-regulating biological concept adopted from the Physarum model, thereby allowing the identification of optimal paths that are independent of the stated assumption. Network hubs and bridges were investigated in structural brain networks using the Physarum model. The optimal paths and fluid flow were used to formulate the Physarum centrality measure. Most network hubs and bridges are overlapped to some extent, but those based on Physarum centrality contain local and global information in the superior frontal, anterior cingulate, middle temporal gyrus, and precuneus regions. This approach also reduced individual variation. Our results suggest that the Physarum centrality presents a trade-off between the degree and betweenness centrality measures.

Brain structural changes after multi-strategic metamemory training in older adults with subjective memory complaints: A randomized controlled trial.

BACKGROUND: Metamemory is the process of monitoring and controlling one's memory. Improving metamemory may reduce the memory problem in old age. We hypothesized that metamemory training (MMT) would improve cognition in older adults with subjective memory complaints and change the brain region related to metacognition. METHOD: We recruited and randomized older adults to the multi-strategic memory training of 10 weekly 90-min sessions, based on the metamemory concept or usual care. Cognitive tests including the Elderly Verbal Learning Test, Simple Rey Figure Test, Digit Span, Spatial Span, Categorical Fluency, and the Boston Naming Test were done in 201 participants, together with magnetic resonance imaging (MRI) in 49 participants before and after training. RESULTS: A total of 112 in the training group and 89 in the control group participated. The training group had a significant increase in long-term delayed free recall, categorical fluency, and the Boston Naming test. In MRI, the mean diffusivity of the bundles of axon tracts passing from the frontal lobe to the posterior end of the lateral sulcus decreased in the training group. CONCLUSION: These results indicate that the MMT program has a positive impact on enhancing older people' cognitive performance. Improved white matter integrity in the anterior and posterior cerebrum and increased cortical thickness of prefrontal regions, which related to metacognition, possibly suggest that the effects of the MMT would be induced via the enhancement of cognitive control.

Multimodal imaging analyses in patients with genetic and sporadic forms of small vessel disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI). The aim of this study was to compare white matter integrity and cortical thickness between typical CADASIL, a genetic form, and two sporadic forms of SVCI (with NOTCH3 and without NOTCH3 variants). We enrolled typical CADASIL patients (N = 11) and SVCI patients [with NOTCH3 variants (N = 15), without NOTCH3 variants (N = 101)]. To adjust the age difference, which reflects the known difference in clinical and radiologic courses between typical CADASIL patients and SVCI patients, we constructed a W-score of measurement for diffusion tensor image and cortical thickness. Typical CADASIL patients showed more frequent white matter hyperintensities in the bilateral posterior temporal region compared to SVCI patients (p < 0.001, uncorrected). We found that SVCI patients, regardless of the presence of NOTCH3 variants, showed significantly greater microstructural alterations (W-score, p < 0.05, FWE-corrected) and cortical thinning (W-score, p < 0.05, FDR-corrected) than typical CADASIL patients. In this study, typical CADASIL and SVCI showed distinct anatomic vulnerabilities in the cortical and subcortical structures. However, there was no difference between SVCI with NOTCH3 variants and SVCI without NOTCH3 variants.

Vascular Effects on Depressive Symptoms in Cognitive Impairment.

Late life depression is related to pathologic burdens, such as cerebral small vascular disease (CSVD) and amyloid, which are associated with brain network changes and cortical thinning. To examine the associations of various CSVD imaging markers, amyloid, and network changes with depression in cognitively impaired patients, we prospectively recruited 228 cognitively impaired patients having various degrees of amyloid and CSVD who underwent diffuse tensor image and PiB PET. Greater CSVD burden was associated with greater Geriatric Depression Scale (GDS) (white matter hyperintensities, WMH: p = 0.025, lacunes: p < 0.001) but not with amyloid (p = 0.095), and cortical thinning (p = 0.630) was not associated with greater GDS. The changes in white matter networks were related to GDS with decreasing integration (global efficiency: p < 0.001) and increasing segregation (clustering coefficient: p = 0.009). The network changes mediated the relationships of WMH and lacunes with GDS. Our findings provide insight to better understand how CSVD burdens contribute to depression in cognitively impaired patients having varying degrees of amyloid and vascular burdens.

Total MRI Small Vessel Disease Burden Correlates with Cognitive Performance, Cortical Atrophy, and Network Measures in a Memory Clinic Population.

BACKGROUND: Recent evidence suggests that combining individual imaging markers of cerebral small vessel disease (SVD) may more accurately reflect its overall burden and better correlate with clinical measures. OBJECTIVE: We wished to establish the clinical relevance of the total SVD score in a memory clinic population by investigating the association with SVD score and cognitive performance, cortical atrophy, and structural network measures, after adjusting for amyloid-ß burden. METHODS: We included 243 patients with amnestic mild cognitive impairment (MCI), Alzheimer's disease dementia, subcortical vascular MCI, or subcortical vascular dementia. All underwent MR and [11C] PiB-PET scanning and had standardized cognitive testing. Multiple linear regression was used to evaluate the relationships between SVD score and cognition, cortical thickness, and structural network measures. Path analyses were performed to evaluate whether network disruption mediates the effects of SVD score on cortical thickness and cognition. RESULTS: Total SVD score was associated with the performance of frontal (ß - 4.31, SE 2.09, p = 0.040) and visuospatial (ß - 0.95, SE 0.44, p = 0.032) tasks, and with reduced cortical thickness in widespread brain regions. Total SVD score was negatively correlated with nodal efficiency, as well as changes in brain network organization, with evidence of reduced integration and increasing segregation. Path analyses showed that the associations between SVD score and frontal and visuospatial scores were partially mediated by decreases in their corresponding nodal efficiency and cortical thickness. CONCLUSION: Total SVD burden has clinical relevance in a memory clinic population and correlates with cognition, and cortical atrophy, as well as structural network disruption.

Evaluation of Cerebral White Matter in Prelingually Deaf Children Using Diffusion Tensor Imaging.

This study compared white matter development in prelingually deaf and normal-hearing children using a tract-based spatial statistics (TBSS) method. Diffusion tensor imaging (DTI) was performed in 21 prelingually deaf (DEAF group) and 20 normal-hearing (HEAR group) subjects aged from 1.7 to 7.7 years. Using TBSS, we evaluated the regions of significant difference in fractional anisotropy (FA) between the groups. Correlations between FA values and age in each group were also analyzed using voxel-wise correlation analyses on the TBSS skeleton. Lower FA values of the white matter tract of Heschl's gyrus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the superior longitudinal fasciculus, and the forceps major were evident in the DEAF group compared with those in the HEAR group below 4 years of age, while the difference was not significant in older subjects. We also found that age-related development of the white matter tracts may continue until 8 years of age in deaf children. These results imply that development of the cerebral white matter tracts is delayed in prelingually deaf children.