The connectional anatomy of visual mental imagery: evidence from a patient with left occipito-temporal damage.

Most of us can use our "mind's eye" to mentally visualize things that are not in our direct line of sight, an ability known as visual mental imagery. Extensive left temporal damage can impair patients' visual mental imagery experience, but the critical locus of lesion is unknown. Our recent meta-analysis of 27 fMRI studies of visual mental imagery highlighted a well-delimited region in the left lateral midfusiform gyrus, which was consistently activated during visual mental imagery, and which we called the Fusiform Imagery Node (FIN). Here, we describe the connectional anatomy of FIN in neurotypical participants and in RDS, a right-handed patient with an extensive occipito-temporal stroke in the left hemisphere. The stroke provoked right homonymous hemianopia, alexia without agraphia, and color anomia. Despite these deficits, RDS had normal subjective experience of visual mental imagery and reasonably preserved behavioral performance on tests of visual mental imagery of object shape, object color, letters, faces, and spatial relationships. We found that the FIN was spared by the lesion. We then assessed the connectional anatomy of the FIN in the MNI space and in the patient's native space, by visualizing the fibers of the inferior longitudinal fasciculus (ILF) and of the arcuate fasciculus (AF) passing through the FIN. In both spaces, the ILF connected the FIN with the anterior temporal lobe, and the AF linked it with frontal regions. Our evidence is consistent with the hypothesis that the FIN is a node of a brain network dedicated to voluntary visual mental imagery. The FIN could act as a bridge between visual information and semantic knowledge processed in the anterior temporal lobe and in the language circuits.

Grey Matter Loss at Different Stages of Cognitive Decline: A Role for the Thalamus in Developing Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive impairment and large loss of grey matter volume and is the most prevalent form of dementia worldwide. Mild cognitive impairment (MCI) is the stage that precedes the AD dementia stage, but individuals with MCI do not always convert to the AD dementia stage, and it remains unclear why. OBJECTIVE: We aimed to assess grey matter loss across the brain at different stages of the clinical continuum of AD to gain a better understanding of disease progression. METHODS: In this large-cohort study (N = 1,386) using neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative, voxel-based morphometry analyses were performed between healthy controls, individuals with early and late and AD dementia stage. RESULTS: Clear patterns of grey matter loss in mostly hippocampal and temporal regions were found across clinical stages, though not yet in early MCI. In contrast, thalamic volume loss seems one of the first signs of cognitive decline already during early MCI, whereas this volume loss does not further progress from late MCI to AD dementia stage. AD dementia stage converters already show grey matter loss in hippocampal and mid-temporal areas as well as the posterior thalamus (pulvinar) and angular gyrus at baseline. CONCLUSION: This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Regional microglial populations in central autonomic brain regions in SUDEP.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) may arise as a result of autonomic dysfunction during a seizure. The central autonomic networks (CANs) modulate brainstem cardiorespiratory regulation. Recent magnetic resonance imaging (MRI) studies in SUDEP have shown cortical and subcortical volume changes and altered connectivity between CAN regions, but the pathological correlate is unknown. Because neuroinflammation is both a cause and a consequence of seizures and may relate to regional brain pathology, our aim was to evaluate microglial populations in CANs in SUDEP. METHODS: In 55 postmortem cases, including SUDEP, epilepsy controls without SUDEP and nonepilepsy controls, we quantified Iba1-expressing microglia in 14 cortical and thalamic areas that included known CAN regions. RESULTS: Mean Iba1 labeling across all brain regions was significantly higher in SUDEP cases compared to epilepsy and nonepilepsy controls. There was significant regional variation in Iba1 labeling in SUDEP cases only, with highest labeling in the medial thalamus. Significantly higher labeling in SUDEP cases than epilepsy and nonepilepsy controls was consistently noted in the superior temporal gyrus. In cases with documented seizures up to 10 days prior to death, significantly higher mean Iba1 labeling was observed in SUDEP compared to epilepsy controls. SIGNIFICANCE: Our findings support microglial activation in SUDEP, including cortical and subcortical regions with known autonomic functions such as the thalamus and superior temporal gyrus. This may be relevant to cellular pathomechanisms underlying cardioregulatory failure during a seizure.

Neonatal valproic acid exposure produces altered gyrification related to increased parvalbumin-immunopositive neuron density with thickened sulcal floors.

Valproic acid (VPA) treatment is associated with autism spectrum disorder in humans, and ferrets can be used as a model to test this; so far, it is not known whether ferrets react to developmental VPA exposure with gyrencephalic abnormalities. The current study characterized gyrification abnormalities in ferrets following VPA exposure during neonatal periods, corresponding to the late stage of cortical neurogenesis as well as the early stage of sulcogyrogenesis. Ferret pups received intraperitoneal VPA injections (200 µg/g of body weight) on postnatal days (PD) 6 and 7. BrdU was administered simultaneously at the last VPA injection. Ex vivo MRI-based morphometry demonstrated significantly lower gyrification index (GI) throughout the cortex in VPA-treated ferrets (1.265 ± 0.027) than in control ferrets (1.327 ± 0.018) on PD 20, when primary sulcogyrogenesis is complete. VPA-treated ferrets showed significantly smaller sulcal-GIs in the rostral suprasylvian sulcus and splenial sulcus but a larger lateral sulcus surface area than control ferrets. The floor cortex of the inner stratum of both the rostral suprasylvian and splenial sulci and the outer stratum of the lateral sulcus showed a relatively prominent expansion. Parvalbumin-positive neuron density was significantly greater in the expanded cortical strata of sulcal floors in VPA-treated ferrets, regardless of the BrdU-labeled status. Thus, VPA exposure during the late stage of cortical neurogenesis may alter gyrification, primarily in the frontal and parietotemporal cortical divisions. Altered gyrification may thicken the outer or inner stratum of the cerebral cortex by increasing parvalbumin-positive neuron density.

Cerebellar-limbic neurocircuit is the novel biosignature of physio-cognitive decline syndrome.

Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.

Vocal music enhances memory and language recovery after stroke: pooled results from two RCTs.

OBJECTIVE: Previous studies suggest that daily music listening can aid stroke recovery, but little is known about the stimulus-dependent and neural mechanisms driving this effect. Building on neuroimaging evidence that vocal music engages extensive and bilateral networks in the brain, we sought to determine if it would be more effective for enhancing cognitive and language recovery and neuroplasticity than instrumental music or speech after stroke. METHODS: Using data pooled from two single-blind randomized controlled trials in stroke patients (N = 83), we compared the effects of daily listening to self-selected vocal music, instrumental music, and audiobooks during the first 3 poststroke months. Outcome measures comprised neuropsychological tests of verbal memory (primary outcome), language, and attention and a mood questionnaire performed at acute, 3-month, and 6-month stages and structural and functional MRI at acute and 6-month stages. RESULTS: Listening to vocal music enhanced verbal memory recovery more than instrumental music or audiobooks and language recovery more than audiobooks, especially in aphasic patients. Voxel-based morphometry and resting-state and task-based fMRI results showed that vocal music listening selectively increased gray matter volume in left temporal areas and functional connectivity in the default mode network. INTERPRETATION: Vocal music listening is an effective and easily applicable tool to support cognitive recovery after stroke as well as to enhance early language recovery in aphasia. The rehabilitative effects of vocal music are driven by both structural and functional plasticity changes in temporoparietal networks crucial for emotional processing, language, and memory.

Abnormal pain perception is associated with thalamo-cortico-striatal atrophy in C9orf72 expansion carriers in the GENFI cohort.

OBJECTIVE: Frontotemporal dementia (FTD) is typically associated with changes in behaviour, language and movement. However, recent studies have shown that patients can also develop an abnormal response to pain, either heightened or diminished. We aimed to investigate this symptom in mutation carriers within the Genetic FTD Initiative (GENFI). METHODS: Abnormal responsiveness to pain was measured in 462 GENFI participants: 281 mutation carriers and 181 mutation-negative controls. Changes in responsiveness to pain were scored as absent (0), questionable or very mild (0.5), mild (1), moderate (2) or severe (3). Mutation carriers were classified into C9orf72 (104), GRN (128) and MAPT (49) groups, and into presymptomatic and symptomatic stages. An ordinal logistic regression model was used to compare groups, adjusting for age and sex. Voxel-based morphometry was performed to identify neuroanatomical correlates of abnormal pain perception. RESULTS: Altered responsiveness to pain was present to a significantly greater extent in symptomatic C9orf72 expansion carriers than in controls: mean score 0.40 (SD 0.71) vs 0.00 (0.04), reported in 29% vs 1%. No significant differences were seen between the other symptomatic groups and controls, or any of the presymptomatic mutation carriers and controls. Neural correlates of altered pain perception in C9orf72 expansion carriers were the bilateral thalamus and striatum as well as a predominantly right-sided network of regions involving the orbitofrontal cortex, inferomedial temporal lobe and cerebellum. CONCLUSION: Changes in pain perception are a feature of C9orf72 expansion carriers, likely representing a disruption in somatosensory, homeostatic and semantic processing, underpinned by atrophy in a thalamo-cortico-striatal network.

Hsp90 inhibitor HSP990 in very low dose upregulates EAAT2 and exerts potent antiepileptic activity.

Rationale: Dysfunction or reduced levels of EAAT2 have been documented in epilepsy. We previously demonstrated the antiepileptic effects of Hsp90 inhibitor 17AAG in temporal lobe epilepsy by preventing EAAT2 degradation. Because of the potential toxicities of 17AAG, this study aimed to identify an alternative Hsp90 inhibitor with better performance on Hsp90 inhibition, improved blood-brain barrier penetration and minimal toxicity. Methods: We used cell-based screening and animal models of epilepsy, including mouse models of epilepsy and Alzheimer's disease, and a cynomolgus monkey model of epilepsy, to evaluate the antiepileptic effects of new Hsp90 inhibitors. Results: In both primary cultured astrocytes and normal mice, HSP990 enhanced EAAT2 levels at a lower dose than other Hsp90 inhibitors. In epileptic mice, administration of 0.1 mg/kg HSP990 led to upregulation of EAAT2 and inhibition of spontaneous seizures. Additionally, HSP990 inhibited seizures and improved cognitive functions in the APPswe/PS1dE9 transgenic model of Alzheimer's disease. In a cynomolgus monkey model of temporal lobe epilepsy, oral administration of low-dose HSP990 completely suppressed epileptiform discharges for up to 12 months, with no sign of hepatic and renal toxicity. Conclusions: These results support further preclinical studies of HSP990 treatment for temporal lobe epilepsy.

Characterising the brain metalloproteome in Down syndrome patients with concomitant Alzheimer's pathology.

Down syndrome (DS) is a common intellectual disability, with an incidence of 1 in 700 and is caused by trisomy 21. People with DS develop Alzheimer's disease (AD)-like neuropathology by the age of 40. As metal ion dyshomeostasis (particularly zinc, iron and copper) is one of the characteristics of AD and is believed to be involved in the pathogenesis of disease, we reasoned that it may also be altered in DS. Thus, we used inductively coupled plasma mass spectrometry to examine metal levels in post-mortem brain tissue from DS individuals with concomitant AD pathology. Size exclusion-ICPMS was also utilised to characterise the metalloproteome in these cases. We report here for the first time that iron levels were higher in a number of regions in the DS brain, including the hippocampus (40%), frontal cortex (100%) and temporal cortex (34%), compared to controls. Zinc and copper were also elevated (both 29%) in the DS frontal cortex, but zinc was decreased (23%) in the DS temporal cortex. Other elements were also examined, a number of which also showed disease-specific changes. The metalloproteomic profile in the DS brain was also different to that in the controls. These data suggest that metals and metal:protein interactions are dysregulated in the DS brain which, given the known role of metals in neurodegeneration and AD, is likely to contribute to the pathogenesis of disease. Interrogation of the underlying cellular mechanisms and consequences of this failure in metal ion homeostasis, and the specific contributions of the individual DS and AD phenotypes to these changes, should be explored.

Changes in the development of subcortical structures in autism spectrum disorder.

Many studies have reported abnormalities in the volume of subcortical structures in individuals with autism spectrum disorder (ASD), and many of these change with age. However, most studies that have investigated subcortical structures were cross-sectional and did not accurately segment the subcortical structures. In this study, we used volBrain, an automatic and reliable quantitative analysis tool, and a longitudinal design to examine developmental changes in the volume of subcortical structures in ASD, and quantified the relation between subcortical volume development and clinical correlates. Nineteen individuals with ASD (16 males; age: 12.53 ± 2.34 years at baseline; interval: 2.33 years) and 14 typically developing controls (TDC; 12 males; age: 13.50 ± 1.77 years at baseline; interval: 2.31 years) underwent T1-weighted MRI at two time points. Bilaterally, hippocampus volume increased from baseline to follow-up in both ASD and TDC, with no difference between groups. Left caudate and right thalamus volume decreased in ASD, but did not change in TDC. The decreases in left caudate and right thalamus volume were related to ASD social score. Right amygdala volume was larger in ASD than in TDC at baseline but not at follow-up. These results confirm previous cross-sectional findings regarding the development of subcortical structures in ASD. The association between developmental changes in left caudate and right thalamus volume and ASD social score offers an explanation for the social deficits in ASD. Results also captured the different abnormality of amygdala volume between childhood and late adolescence.

Cortical network underlying audiovisual semantic integration and modulation of attention: An fMRI and graph-based study.

Many neuroimaging and electrophysiology studies have suggested that semantic integration as a high-level cognitive process involves various cortical regions and is modulated by attention. However, the cortical network specific to semantic integration and the modulatory mechanism of attention remain unclear. Here, we designed an fMRI experiment using "bimodal stimulus" to extract information regarding the cortical activation related to the effects of semantic integration with and without attention, and then analyzed the characteristics of the cortical network and the modulating effect of attention on semantic integration. To further investigate the related cortical regions, we constructed a functional brain network for processing attended AV stimuli to evaluate the nodal properties using a graph-based method. The results of the fMRI and graph-based analyses showed that the semantic integration with attention activated the anterior temporal lobe (ATL), temporoparietal junction (TPJ), and frontoparietal cortex, with the ATL showing the highest nodal degree and efficiency; in contrast, semantic integration without attention involved a relatively small cortical network, including the posterior superior temporal gyrus (STG), Heschl's gyrus (HG), and precentral gyrus. These results indicated that semantic integration is a complex cognitive process that occurs not only in the attended condition but also in the unattended condition, and that attention could modulate the distribution of cortical networks related to semantic integration. We suggest that semantic integration with attention is a conscious process and needs a wide cortical network working together, in which the ATL plays the role of a central hub; in contrast, semantic integration without attention is a pre-attentive process and involves a relatively smaller cortical network, in which the HG may play an important role. Our study will provide valuable insights into semantic integration and will be useful for investigations on multisensory integration and attention mechanism at multiple processing stages and levels within the cortical hierarchy.

Hippocampus-driving progressive structural alterations in medication-naïve major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with abnormalities in brain structure. However, structural abnormality findings have been inconsistent and how structural changes lead to progressive morphometric alterations in depressed brain regions remains unclear. METHODS: High-resolution T1-weighted magnetic resonance images of first-episode medication-naïve MDD patients (20 men, 36 women) and healthy control participants (33 men, 23 women) were evaluated. Voxel-based morphometry analysis was conducted based on T1-weighted images. The causal network of structural covariance analysis (CaSCN) was accomplished by applying Granger causality analysis to the sequenced T1-weighted images in order to assess causal effect of structural changes. RESULTS: When comparing MDD patients and healthy controls, gray matter was greater in the bilateral amygdala, the bilateral hippocampus, the left parahippocampus, and the right fusiform, while it was lessened in the bilateral brainstem, the bilateral pallidum, and the bilateral thalamus. Selecting the hippocampus as the seed region to run further CaSCN analysis revealed that the hippocampus is a prominent node that exerts a causal effect on the amygdala and regions of the default mode network. LIMITATIONS: Our sample size was small and the subjects groups' ages were not well matched. We also recognize that the hippocampus is not necessarily the original source of brain network alteration in MDD. CONCLUSIONS: The CaSCN clarified the causal relationship between progressive gray matter alterations in the hippocampus and in other regions. Our work provided evidence of a network spread mechanism in terms of the causal influence of hippocampal alteration on progressive brain structural alterations in MDD.

Brain structural abnormalities as potential markers for detecting individuals with ultra-high risk for psychosis: A systematic review and meta-analysis.

OBJECTIVE: This study aims to determine whether structural alterations can be used as neuroimaging markers to detect individuals with ultra-high risk (UHR) for psychosis for the diagnosis of schizophrenia and improvement of treatment outcomes. METHODS: Embase and Pubmed databases were searched for related studies in July 2018. The search was performed without restriction on time and regions or languages. A total of 188 articles on voxel-based morphometry (VBM) and 96 articles on cortical thickness were obtained, and another 6 articles were included after the reference lists were checked. Our researchers assessed and extracted the data in accordance with the PRISMA guideline. The data were processed with a seed-based mapping method. RESULTS: Fourteen VBM and nine cortical thickness studies were finally included in our study. In individuals with UHR, the gray matter volumes in the bilateral median cingulate (Z = 1.034), the right fusiform gyrus (Z = 1.051), the left superior temporal gyrus (Z = 1.048), and the right thalamus (Z = 1.039) increased relative to those of healthy controls. By contrast, the gray matter volumes in the right gyrus rectus (Z = -2.109), the right superior frontal gyrus (Z = -2.321), and the left superior frontal gyrus (Z = -2.228) decreased. The robustness of these findings was verified through Jackknife sensitivity analysis, and heterogeneity across studies was low. Typically, cortical thickness alterations were not detected in individuals with UHR. CONCLUSIONS: Structural abnormalities of the thalamocortical circuit may underpin the neurophysiology of psychosis and mark the vulnerability of transition to psychosis in UHR subjects.

Saikosaponin­D improves fear memory deficits in ovariectomized rats via the action of estrogen receptor­α in the hippocampus.

Saikosaponin­D (SSD), which is the main bioactive component in the traditional Chinese medicine Chai Hu (Bupleurum falcatum L), possesses estrogen­like properties and is widely used in treating estrogen­related neurological disorders. The current study aimed to investigate the protective effects of SSD on the fear memory deficit in ovariectomized (OVX) rats and the potential underlying mechanism. SSD treatment significantly prolonged freezing time in OVX rats in a manner similar to that of estradiol (E2), whereas this effect was markedly suppressed by co­administration of ICI182780, a non­selective estrogen receptor (ER) inhibitor. The expression of ERα in the hippocampus of OVX rats was significantly elevated by SSD; however, Erß expression and E2 synthesis were not markedly affected by SSD treatment. Collectively, this study demonstrated that SSD­mediated fear memory improvement in OVX rats may be attributed not to E2 levels or ERß activity, but to ERα activation in the hippocampus.

HIV infection and age effects on striatal structure are additive.

The age of the HIV-infected population is increasing. Although many studies document gray matter volume (GMV) changes following HIV infection, GMV also declines with age. Findings have been inconsistent concerning interactions between HIV infection and age on brain structure. Effects of age, substance use, and inadequate viral suppression may confound identification of GMV serostatus effects using quantitative structural measures. In a cross-sectional study of HIV infection, including 97 seropositive and 84 seronegative, demographically matched participants, ages 30-70, we examined serostatus and age effects on GMV and neuropsychological measures. Ninety-eight percent of seropositive participants were currently treated with anti-retroviral therapies and all were virally suppressed. Gray, white, and CSF volumes were estimated using high-resolution T1-weighted MRI. Linear regression modeled effects of serostatus, age, education, comorbidities, and magnetic field strength on brain structure, using both a priori regions and voxel-based morphometry. Although seropositive participants exhibited significant bilateral decreases in striatal GMV, no serostatus effects were detected in the thalamus, hippocampus, or cerebellum. Age was associated with cortical, striatal, thalamic, hippocampal, and cerebellar GMV reductions. Effects of age and serostatus on striatal GMV were additive. Although no main effects of serostatus on neuropsychological performance were observed, serostatus moderated the relationship between pegboard performance and striatal volume. Both HIV infection and age were associated with reduced striatal volume. The lack of interaction of these two predictors suggests that HIV infection is associated with premature, but not accelerated, brain age. In serostatus groups matched on demographic and clinical variables, there were no observed differences in neuropsychological performance. Striatal GMV measures may be promising biomarker for use in studies of treated HIV infection.

Nuclei-specific thalamic connectivity predicts seizure frequency in drug-resistant medial temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: We assessed correlations between the resting state functional connectivity (RSFC) of different thalamic nuclei and seizure frequency in patients with drug-resistant medial temporal lobe epilepsy (mTLE). METHODS: Seventeen patients with mTLE and 17 sex-/age-/handedness-matched controls participated. A seed-based correlation method for the resting-state FMRI data was implemented to get RSFC maps of 70 thalamic nuclei seed masks. Group statistics for individual RSFC for subjects and seed masks were performed to obtain within-group characteristics and between-group differences with age covariates. A linear regression was applied to test whether seizure frequency correlated with thalamic nuclear RSFC with the whole brain in mTLE patients. RESULTS: RSFC of thalamic nuclei showed spatially distinguishable connectivity patterns that reflected principal inputs and outputs that were derived from priori anatomical knowledge. We found group differences between normal control and mTLE groups in RSFC for nuclei seeds located in various subdivisions of thalamus. The RSFCs in some of those nuclei were strongly correlated with seizure frequency. CONCLUSIONS: Mediodorsal thalamic nuclei may play important roles in seizure activity or in the regulation of neuronal activity in the limbic system. The RSFC of motor- and sensory-relay nuclei may help elucidate sensory-motor deficits associated with chronic seizure activity. RSFC of the pulvinar nuclei of the thalamus could also be a key reflection of symptom-related functional deficits in mTLE.

[Time and Self in Episodic Memory and Confabulation].

Confabulation is defined as the production of narrative descriptions of events that never happened, and is often observed in amnesia with basal forebrain lesions. However, little is known about the possible mechanisms related to confabulation. In this review article, we summarized previous neuropsychological and neuroimaging studies associated with confabulation, and proposed a hypothetical mechanism of confabulation. Previous studies have demonstrated that amnesic patients with confabulation after basal forebrain damage are impaired in the processing of time-related information in episodic memory and that activation of this region is significant during the processing of time-related information in episodic memory. In addition, confabulating patients with basal forebrain lesions extending to the medial prefrontal cortex (mPFC), medial temporal, and thalamic regions are likely to show significant disturbances in age-awareness and significant false memories in personally experienced events. Given the importance of the mPFC in the self-referential process and of the hippocampus in the integration of episodic components, the basal forebrain region could play an important role in orienting the self in time by acting as an interface between the mPFC and the hippocampus. Confabulation in basal forebrain amnesia could be caused by a decline of the time-self interaction.

Neuroimaging Determinants of Poststroke Cognitive Performance.

Background and Purpose- We aimed to define the neuroimaging determinants of poststroke cognitive performance and their relative contributions among a spectrum of magnetic resonance imaging markers, including lesion burden and strategic locations. Methods- We prospectively included patients with stroke from the GRECogVASC study (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) who underwent 3-T magnetic resonance imaging and a comprehensive standardized battery of neuropsychological tests 6 months after the index event. An optimized global cognitive score and neuroimaging markers, including stroke characteristics, cerebral atrophy markers, and small vessel diseases markers, were assessed. Location of strategic strokes was determined using a specifically designed method taking into account stroke size and cerebral atrophy. A stepwise multivariable linear regression model was used to identify magnetic resonance imaging determinants of cognitive performance. Results- Data were available for 356 patients (mean age: 63.67±10.6 years; 326 [91.6%] of the patients had experienced an ischemic stroke). Six months poststroke, 50.8% of patients presented with a neurocognitive disorder. Strategic strokes (right corticospinal tract, left antero-middle thalamus, left arcuate fasciculus, left middle frontal gyrus, and left postero-inferior cerebellum; R2=0.225; P=0.0001), medial temporal lobe atrophy ( R2=0.077; P=0.0001), total brain tissue volume ( R2=0.028; P=0.004), and stroke volume ( R2=0.013; P=0.005) were independent determinants of cognitive performance. Strategic strokes accounted for the largest proportion of the variance in the cognitive score (22.5%). The white matter hyperintensity burden, brain microbleeds, and dilated perivascular spaces were not independent determinants. Conclusions- Optimized global cognitive score and combined approach of both quantitative measures related to structure loss and qualitative measures related to the presence of strategic lesion are required to improve the determination of structure-function relationship of cognitive performance after stroke.

Aggressiveness of martial artists correlates with reduced temporal pole grey matter concentration.

Perception and practice of violence have hedonistic aspects associated with positive arousal (appetitive aggression). Earlier studies have mainly investigated the aetiology of aggressive behaviour in forensic/psychiatric patients. The present study examined structural brain characteristics in healthy people practicing violent sports (martial artists) compared to controls not showing violent behaviour. Aggressiveness was assessed in 21 male healthy martial artists and 26 age-matched male healthy controls using the aggressivity factors questionnaire (FAF). Participants underwent structural T1-weighted MRI. Grey matter (GM) differences were analysed using voxel-based morphometry. Whole-brain analyses of the main effects of group and aggressiveness and their interaction were computed. An interaction effect between group and aggressiveness was evident in a brain cluster comprising the left temporal pole and left inferior temporal gyrus. In martial artists, aggressiveness was inversely related to mean GM concentration in this cluster while in controls the opposite pattern was evident. Since these temporal brain regions are relevant for emotion/aggression regulation and threat appraisal, the increased GM concentration in aggressive controls might reflect a stronger cognitive top-down inhibition of their aggressiveness. Lower GM concentration in more aggressive martial artists may indicate a reduced need of inhibitory cognitive control because of their improved self-regulation skills.