Early Cortical Changes Research Articles

Cortical Macro- and Microstructural Changes in Parkinson's Disease with Probable Rapid Eye Movement Sleep Behavior Disorder.

Evidence regarding cortical atrophy patterns in Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-pRBD) remains scarce. Cortical mean diffusivity (cMD), as a novel imaging biomarker highly sensitive to detecting cortical microstructural changes in different neurodegenerative diseases, has not been investigated in PD-pRBD yet. The aim was to investigate cMD as a sensitive measure to identify subtle cortical microstructural changes in PD-pRBD and its relationship with cortical thickness (CTh). Twenty-two PD-pRBD, 31 PD without probable RBD (PD-nonpRBD), and 28 healthy controls (HC) were assessed using 3D T1-weighted and diffusion-weighted magnetic resonance imaging on a 3-T scanner and neuropsychological testing. Measures of cortical brain changes were obtained through cMD and CTh. Two-class group comparisons of a general linear model were performed (P < 0.05). Cohen's d effect size for both approaches was computed. PD-pRBD patients showed higher cMD than PD-nonpRBD patients in the left superior temporal, superior frontal, and precentral gyri, precuneus cortex, as well as in the right middle frontal and postcentral gyri and paracentral lobule (d > 0.8), whereas CTh did not detect significant differences. PD-pRBD patients also showed increased bilateral posterior cMD in comparison with HCs (d > 0.8). These results partially overlapped with CTh results (0.5 < d < 0.8). PD-nonpRBD patients showed no differences in cMD when compared with HCs but showed cortical thinning in the left fusiform gyrus and lateral occipital cortex bilaterally (d > 0.5). cMD may be more sensitive than CTh displaying significant cortico-structural differences between PD subgroups, indicating this imaging biomarker's utility in studying early cortical changes in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

APOE4 affects cortical microstructural alterations in Alzheimer’s disease: evidence from an autopsy‐confirmed cohort

AbstractBackgroundApolipoprotein E e4 (APOE4) is one of the most studied genetic risk factors for developing Alzheimer’s disease (AD). However, it is still not fully understood how APOE4 contributes to cortical neurodegeneration. We investigate ante‐mortem cortical microstructural changes in carrier and non‐carrier patient MRIs with autopsy‐confirmed Alzheimer’s disease neuropathological changes (ADNC).MethodForty‐nine participants with ADNC and ante‐mortem MRI were obtained from the National Alzheimer’s Coordinating Center (NACC; n = 34) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 15). Participants were grouped based on APOE4 presence (22 non‐carriers and 27 carriers). Thal phase, CERAD neuritic plaque assessment, Braak NFT, and combined ABC score, were used as AD neuropathological hallmarks. Structural and diffusion MRI (dMRI) were used to calculate cortical diffusivity measures in five different functional macroregions: Primary Sensory, Unimodal, Limbic/Proisocortex, Heteromodal and Primary Motor (Ffytche &amp; Wible 2014, PMID:24936089; Mesulam 1998, PMID:9648540). For each macroregion, cortical mean diffusivity and three neuropathology‐inspired cortical diffusivity measures were calculated: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD+) (Torso et al. 2022, PMID:36281682). Clinical, demographic and neuropathological data were used to characterize groups (Table). Group differences in diffusion metrics were tested with GLM adjusting for ABC score, interval between MRI scan date and autopsy date, scanner manufacturer, dMRI b‐value, age and sex, with false discovery rate correction (pFDR&lt;0.05).ResultThe cortical diffusivity investigation revealed higher Primary Sensory (auditory, visual, sensory) AngleR values in APOE4 carriers (Figure). The APOE4 carrier group was significantly younger and showed higher Thal phase, CERAD neuritic plaque, Braak stage and ABC scores.ConclusionCortical diffusivity measures can detect differences in cortical microstructure of APOE4 Carrier and Non‐carrier patients, suggesting a wider pattern of cortical damage in APOE4 carriers that involves Primary Sensory areas (lateral occipital, postcentral, pericalcarine, transverse temporal). Consistent with previous findings, the diffusion‐derived metric AngleR appears particularly sensitive to subtle effects, such as the early cortical changes associated with amyloid deposition and neuroinflammation (Torso et al. 2022, PMID:36281682), perhaps linked to the APOE4 modulation of the pattern of cortical microstructural neurodegeneration.

APOE4 affects cortical microstructural alterations in Alzheimer’s disease: evidence from an autopsy‐confirmed cohort.

AbstractBackgroundApolipoprotein E ε4 (APOE4) is one of the most studied genetic risk factors for developing Alzheimer’s disease (AD). However, it is still not fully understood how APOE4 contributes to cortical neurodegeneration. We investigate ante‐mortem cortical microstructural changes in carrier and non‐carrier patient MRIs with autopsy‐confirmed Alzheimer’s disease neuropathological changes (ADNC).MethodForty‐nine participants with ADNC and ante‐mortem MRI were obtained from the National Alzheimer’s Coordinating Center (NACC; n = 34) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 15). Participants were grouped based on APOE4 presence (22 non‐carriers and 27 carriers). Thal phase, CERAD neuritic plaque assessment, Braak NFT, and combined ABC score, were used as AD neuropathological hallmarks.Structural and diffusion MRI (dMRI) were used to calculate cortical diffusivity measures in five different functional macroregions: Primary Sensory, Unimodal, Limbic/Proisocortex, Heteromodal and Primary Motor (Ffytche &amp; Wible 2014, PMID:24936089; Mesulam 1998, PMID:9648540). For each macroregion, cortical mean diffusivity and three neuropathology‐inspired cortical diffusivity measures were calculated: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD+) (Torso et al. 2022, PMID:36281682).Clinical, demographic and neuropathological data were used to characterize groups (Table). Group differences in diffusion metrics were tested with GLM adjusting for ABC score, interval between MRI scan date and autopsy date, scanner manufacturer, dMRI b‐value, age and sex, with false discovery rate correction (pFDR&lt;0.05).ResultThe cortical diffusivity investigation revealed higher Primary Sensory (auditory, visual, sensory) AngleR values in APOE4 carriers (Figure). The APOE4 carrier group was significantly younger and showed higher Thal phase, CERAD neuritic plaque, Braak stage and ABC scores.ConclusionCortical diffusivity measures can detect differences in cortical microstructure of APOE4 Carrier and Non‐carrier patients, suggesting a wider pattern of cortical damage in APOE4 carriers that involves Primary Sensory areas (lateral occipital, postcentral, pericalcarine, transverse temporal).Consistent with previous findings, the diffusion‐derived metric AngleR appears particularly sensitive to subtle effects, such as the early cortical changes associated with amyloid deposition and neuroinflammation (Torso et al. 2022, PMID:36281682), perhaps linked to the APOE4 modulation of the pattern of cortical microstructural neurodegeneration.

Air pollution exposure is associated with widespread cortical thinning in cognitively unimpaired older women

AbstractBackgroundLate‐life ambient air pollution exposures are associated with increased Alzheimer’s disease (AD) risk1. Cortical thinning in temporal areas vulnerable to AD is associated with memory decline, neuropathological changes, and increased AD risk. However, most neuroimaging studies on air pollution neurotoxicity analyzed volumetric indices that are not sensitive to early cortical changes, and focused on discrete regions of interest (ROI) selected a priori rather than taking an ROI approach across the whole brain. Therefore, the mechanisms linking exposures to early neuropathological processes in older age are poorly understood.MethodWe examined data from 1068 cognitively unimpaired women from the Women’s Health Initiative Memory Study who underwent neuroimaging in 2005‐6 (Meanage = 77.8±3.7). Long‐term residential exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were quantified as the 3‐year average of monthly estimates prior to MRI using spatiotemporal models with regionalized universal kriging. Brain scans were processed using FreeSurfer‐v.5.3.0 to estimate cortical thickness in 34 bilateral regions parcellated with the Desikan‐Killiany atlas. Exposure effects on AD‐vulnerable regions were assessed by calculating an AD signature (higher value representing thicker cortices) of surface‐area‐weighted thickness in the bilateral entorhinal, fusiform, inferior temporal, and middle temporal cortices2. We used linear mixed models to estimate exposure effects on standardized regional cortical thickness and the AD signature, adjusting for sociodemographic, lifestyle, and clinical characteristics, and a random effect for scanner manufacturer.ResultAfter adjusting for covariates and multiple comparisons using the False discovery rate (FDR) method, higher exposures to PM2.5 and NO2 were associated with thinner cortices in at least 31 brain regions (FDR‐adjusted p’s&lt;0.05). There were also significant adverse effects of PM2.5 (β = ‐0.055, 95%CI = [‐0.07,‐0.04] per 1µg/m3) and NO2 (β = ‐0.022, 95%CI = [‐0.03,‐0.01] per 1ppb) on the AD signature, equivalent to 1.1 and 0.5 years of aging, respectively. Across all analyses the strongest effects were observed in the frontal lobe, especially the motor cortex.ConclusionIn cognitively unimpaired older women, higher exposures to PM2.5 and NO2 were associated with widespread cortical thinning, including regions sensitive to AD. However, the strongest associations in the frontal lobe suggest a greater impact of air pollution neurotoxicity on brain aging rather than AD risk.

Comprehensive shape analysis of the cortex in Huntington's disease.

The striatum has traditionally been the focus of Huntington's disease research due to the primary insult to this region and its central role in motor symptoms. Beyond the striatum, evidence of cortical alterations caused by Huntington's disease has surfaced. However, findings are not coherent between studies which have used cortical thickness for Huntington's disease since it is the well-established cortical metric of interest in other diseases. In this study, we propose a more comprehensive approach to cortical morphology in Huntington's disease using cortical thickness, sulcal depth, and local gyrification index. Our results show consistency with prior findings in cortical thickness, including its limitations. Our comparison between cortical thickness and local gyrification index underscores the complementary nature of these two measures-cortical thickness detects changes in the sensorimotor and posterior areas while local gyrification index identifies insular differences. Since local gyrification index and cortical thickness measures detect changes in different regions, the two used in tandem could provide a clinically relevant measure of disease progression. Our findings suggest that differences in insular regions may correspond to earlier neurodegeneration and may provide a complementary cortical measure for detection of subtle early cortical changes due to Huntington's disease.

Rapamycin Cannot Reduce Seizure Susceptibility in Infantile Rats with Malformations of Cortical Development Lacking mTORC1 Activation.

The mechanistic target of the rapamycin (mTOR) pathway is involved in cortical development. However, the efficacy of mTOR inhibitors in malformations of cortical dysplasia (MCD) outside of the tuberous sclerosis complex is unknown. We selected the MCD rat model with prenatal MAM exposure to test the efficacy of mTOR inhibitors in MCDs. We explored the early cortical changes of mTOR pathway protein expression in rats aged P15. We also monitored the early treatment effect of the mTOR inhibitor, rapamycin, on N-methyl-D-aspartate (NMDA)-induced spasms at P15 and their behavior in the juvenile stage. In vivo MR spectroscopy was performed after rapamycin treatment and compared with vehicle controls. There was no difference in mTORC1 pathway protein expression between MAM-exposed MCD rats and controls at P15, and prolonged treatment of rapamycin had no impact on NMDA-induced spasms despite poor weight gain. Prenatal MAM-exposed juvenile rats treated with rapamycin showed increased social approaching and freezing behavior during habituation. MR spectroscopy showed altered neurometabolites, including Gln, Glu+Gln, Tau, and Cr. Despite behavioral changes and in vivo neurometabolic alteration with early prolonged rapamycin treatment, rapamycin had no effect on spasms susceptibility in prenatal MAM-exposed infantile rats with MCD without mTORC1 activation. For MAM-exposed MCD rats without mTORC1 activation, treatment options outside of mTOR pathway inhibitors should be explored.

The acute phase protein lactoferrin is a key feature of Alzheimer\u2019s disease and predictor of A\u03b2 burden through induction of APP amyloidogenic processing

Amyloidogenic processing of the amyloid precursor protein (APP) forms the amyloid-β peptide (Aβ) component of pathognomonic extracellular plaques of AD. Additional early cortical changes in AD include neuroinflammation and elevated iron levels. Activation of the innate immune system in the brain is a neuroprotective response to infection; however, persistent neuroinflammation is linked to AD neuropathology by uncertain mechanisms. Non-parametric machine learning analysis on transcriptomic data from a large neuropathologically characterised patient cohort revealed the acute phase protein lactoferrin (Lf) as the key predictor of amyloid pathology. In vitro studies showed that an interaction between APP and the iron-bound form of Lf secreted from activated microglia diverted neuronal APP endocytosis from the canonical clathrin-dependent pathway to one requiring ADP ribosylation factor 6 trafficking. By rerouting APP recycling to the Rab11-positive compartment for amyloidogenic processing, Lf dramatically increased neuronal Aβ production. Lf emerges as a novel pharmacological target for AD that not only modulates APP processing but provides a link between Aβ production, neuroinflammation and iron dysregulation.

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults.

Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42 /Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. We observed a significant CSF Aβ42 /Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.

Cortical Thickness Changes Following Accelerated Neuromodulation Therapy for Treatment-Resistant Depression Predict Depression Scores at One-Month

Accelerated intermittent theta-burst stimulation (aiTBS) is a safe and effective non-invasive neuromodulation therapy for treatment-resistant depression (TRD), yet the mechanisms underlying this effect are not well known. One potential mechanism involves neuroplastic changes to the cortex induced by repetitive stimulation. To assess this, we compared cortical thickness changes from baseline to immediate post-treatment in individuals undergoing aiTBS for TRD in a sham-controlled trial. We also examined the predictive value of early cortical changes on depression scores at one-month post-treatment.

Increased Cortical Thickness in Patients With Major Depressive Disorder Following Antidepressant Treatment

Background Considering the slow-acting properties of traditional antidepressants, an important challenge in the field is the identification of early treatment response biomarkers. Reduced cortical thickness has been reported in neuroimaging studies of depression. However, little is known whether antidepressants reverse this abnormality. In this brief report, we investigated early cortical thickness changes following treatment with sertraline compared to placebo. Methods Participants (n = 215) with major depressive disorder were randomized to a selective serotonin reuptake inhibitor, sertraline, or to placebo. Structural magnetic resonance imaging scans were acquired at baseline and one week following treatment. Response was defined as at least 50% improvement in Hamilton rating scale for depression score at week 8. In a vertex-wise approach, we examined the effects of treatment, response, and treatment × response. Results Following correction for multiple comparisons, we found a significant effect of treatment, with widespread increase in cortical thickness following sertraline compared to placebo. Clusters with increased thickness were found in the left medial prefrontal cortex, right medial and lateral prefrontal cortex, and within the right parieto-temporal lobes. There were no sertraline-induced cortical thinning, and no significant response effects or treatment × response interactions. Conclusion Our findings suggest that cortical thickness abnormalities may be responsive to antidepressant treatment. However, a relationship between these early cortical changes and later treatment response was not demonstrated. Future studies would be needed to investigate whether those early effects are maintained at eight weeks and are associated with enhanced response.

Brain Aging: Uncovering Cortical Characteristics of Healthy Aging in Young Adults.

Despite extensive research in the field of aging neuroscience, it still remains unclear whether age related cortical changes can be detected in different functional networks of younger adults and whether these networks respond identically to healthy aging. We collected high-resolution brain anatomical data from 56 young healthy adults (mean age = 30.8 ± 8.1 years, 29 males). We performed whole brain parcellation into seven functional networks, including visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal and default mode networks. We estimated intracranial volume (ICV) and averaged cortical thickness (CT), cortical surface area (CSA) and cortical volume (CV) over each hemisphere as well as for each network. Averaged cortical measures over each hemisphere, especially CT and CV, were significantly lower in older individuals compared to younger ones (one-way ANOVA, p < 0.05, corrected for multiple comparisons). There were negative correlations between age and averaged CT and CV over each hemisphere (p < 0.05, corrected for multiple comparisons) as well as between age and ICV (p = 0.05). Network level analysis showed that age was negatively correlated with CT for all functional networks (p < 0.05, corrected for multiple comparisons), apart from the limbic network. While age was unrelated to CSA, it was negatively correlated with CV across several functional networks (p < 0.05, corrected for multiple comparisons). We also showed positive associations between CV and CT and between CV and CSA for all networks (p < 0.05, corrected for multiple comparisons). We interpret the lack of association between age and CT of the limbic network as evidence that the limbic system may be particularly resistant to age-related declines during this period of life, whereas the significant age-related declines in averaged CT over each hemisphere as well as in all other six networks suggests that CT may serve as a reliable biomarker to capture the effect of normal aging. Due to the simultaneous dependence of CV on CT and CSA, CV was unable to identify such effects of normal aging consistently for the other six networks, but there were negative associations observed between age and averaged CV over each hemisphere as well as between age and ICV. Our findings suggest that the identification of early cortical changes within various functional networks during normal aging might be useful for predicting the effect of aging on the efficiency of functional performance even during early adulthood.

Thinner cortex in patients with subjective cognitive decline is associated with steeper decline of memory

We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2–8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini–Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p < 0.05FDR). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease.

Early Cortical Changes in Gamma Oscillations in Alzheimer's Disease.

The entorhinal cortices in the temporal lobe of the brain are key structures relaying memory related information between the neocortex and the hippocampus. The medial entorhinal cortex (MEC) routes spatial information, whereas the lateral entorhinal cortex (LEC) routes predominantly olfactory information to the hippocampus. Gamma oscillations are known to coordinate information transfer between brain regions by precisely timing population activity of neuronal ensembles. Here, we studied the organization of in vitro gamma oscillations in the MEC and LEC of the transgenic (tg) amyloid precursor protein (APP)-presenilin 1 (PS1) mouse model of Alzheimer’s Disease (AD) at 4–5 months of age. In vitro gamma oscillations using the kainate model peaked between 30–50 Hz and therefore we analyzed the oscillatory properties in the 20–60 Hz range. Our results indicate that the LEC shows clear alterations in frequency and power of gamma oscillations at an early stage of AD as compared to the MEC. The gamma-frequency oscillation slows down in the LEC and also the gamma power in dorsal LEC is decreased as early as 4–5 months in the tg APP-PS1 mice. The results of this study suggest that the timing of olfactory inputs from LEC to the hippocampus might be affected at an early stage of AD, resulting in a possible erroneous integration of the information carried by the two input pathways to the hippocampal subfields.

Relation between clinical risk factors, early cortical changes, and neurodevelopmental outcome in preterm infants

Cortical folding mainly takes place in the third trimester of pregnancy and may therefore be influenced by preterm birth. The aim of this study was to evaluate the development of specific cortical structures between early age (around 30weeks postmenstrual age) and term-equivalent age (TEA, around 40weeks postmenstrual age) in 71 extremely preterm infants, and to associate this to clinical characteristics and neurodevelopmental outcome at two years of age. First, analysis showed that the central sulcus (CS), lateral fissure (LF) and insula (INS) were present at early MRI in all infants, whereas the other sulci (post-central sulcus [PCS], superior temporal sulcus [STS], superior [SFS] and inferior [IFS] frontal sulcus) were only seen in part of the infants. Relative growth from early to TEA examination was largest in the SFS. A rightward asymmetry of the surface area was seen in development between both examinations except for the LF, which showed a leftward asymmetry at both time points. Second, lower birth weight z-score, multiple pregnancy and prolonged mechanical ventilation showed negative effects on cortical folding of the CS, LF, INS, STS and PCS, mainly on the first examination, suggesting that sulci developing the earliest were the most affected by clinical factors. Finally, in this cohort, a clear association between cortical folding and neurodevelopmental outcome at two years corrected age was found, particularly for receptive language.

Early cortical thickness change after mild traumatic brain injury following motor vehicle collision.

In a motor vehicle collision (MVC), survivors often receive mild traumatic brain injuries (mTBI). Although there have been some reports of early white matter changes after an mTBI, much less is known about early cortical structural changes. To investigate early cortical changes within a few days after an MVC, we compared cortical thickness of mTBI survivors with non-mTBI survivors, then reexamined cortical thickness in the same survivors 3 months later. MVC survivors were categorized as mTBI or non-mTBI based on concussive symptoms documented in emergency departments (EDs). Cortical thickness was measured from MRI images using FreeSurfer within a few days and again at 3 months after MVC. Post-traumatic stress symptoms and physical conditions were also assessed. Compared with the non-mTBI group (n = 23), the mTBI group (n = 21) had thicker cortex in the left rostral middle frontal (rMFG) and right precuneus gyri, but thinner cortex in the left posterior middle temporal gyrus at 7.2 ± 3.1 days after MVC. After 3 months, cortical thickness had decreased in left rMFG in the mTBI group but not in the non-mTBI group. The cortical thickness of the right precuneus region in the initial scans was positively correlated with acute traumatic stress symptoms for all survivors and with the number of reduced activity days for mTBI survivors who completed the follow-up. The preliminary results suggest that alterations in cortical thickness may occur at an early stage of mTBI and that frontal cortex structure may change dynamically over the initial 3 months after mTBI.

CERAD Neuropsychological Total Scores Reflect Cortical Thinning in Prodromal Alzheimer's Disease

Background: Sensitive cognitive global scores are beneficial in screening and monitoring for prodromal Alzheimer's disease (AD). Early cortical changes provide a novel opportunity for validating established cognitive total scores against the biological disease markers. Methods: We examined how two different total scores of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and the Mini-Mental State Examination (MMSE) are associated with cortical thickness (CTH) in mild cognitive impairment (MCI) and prodromal AD. Cognitive and magnetic resonance imaging (MRI) data of 22 progressive MCI, 78 stable MCI, and 98 control subjects, and MRI data of 103 AD patients of the prospective multicenter study were analyzed. Results: CERAD total scores correlated with mean CTH more strongly (r = 0.34-0.38, p < 0.001) than did MMSE (r = 0.19, p = 0.01). Of those vertex clusters that showed thinning in progressive MCI, 60-75% related to the CERAD total scores and 3% to the MMSE. Conclusion: CERAD total scores are sensitive to the CTH signature of prodromal AD, which supports their biological validity in detecting early disease-related cognitive changes.

Neural correlates of cognitive decline in ALS: An fNIRS study of the prefrontal cortex

Functional near infrared spectroscopy (fNIRS) is a clinically feasible functional neuroimaging modality for detecting early cortical changes due to neurodegenerative diseases that affect cognition. The objective of this preliminary investigation was to test for reduced prefrontal activity in persons with cognitive impairments due to amyotrophic lateral sclerosis (ALS). Participants were required to complete two N-back working memory tasks of increasing complexity during fNIRS recordings. Five participants with ALS and age- and gender-matched healthy participants comprised the experimental and control groups, respectively. Significant reductions in prefrontal oxygenation levels were observed for the left and right hemispheres in the ALS group compared to the control group. Reduced prefrontal activation despite intact behavioral performance for a working memory task may suggest early neuroanatomical, neurophysiological and/or compensatory mechanisms in affected individuals. The fNIRS-derived oxygenation measure shows promise as a sensitive neural marker to identify early neuropsychological impairments due to ALS.

Bone Structure Changes in Iliac Crest Grafts Combined with Implants

Remodeling of onlay grafts combined with implants to the mandible results in predictable changes in the graft's radiographic density. We studied the relationship between changes in radiographic density and trabecular structure during the first year after onlay grafting with simultaneous implant placement to the mandible. The aim of this study was to evaluate changes in bone structure after onlay grafting. Standardized extraoral radiographs were taken regularly of 16 mandibular sides. Bone structure was measured using the Carl Zeiss Vision KS 400 3.0 imaging system. The parameters studied were trabecular area and perimeter, cavity area and perimeter, end points, branching points, skeleton length, branch angle and direction, and texture. No differences were found between measurements ventrally versus dorsally of the implant, nor close to versus away from the implant. Early cortical changes suggest partial resorption and formation of a more complex structure. In the fourth quarter after surgery, progressive resorption is seen in the graft's upper cortex. In the graft's upper spongiosa, most parameters indicate bone formation during the first postoperative year. Loading-induced structure changes could not yet be found. The technique can be used to study changes in the architecture of bone grafts. Changes found in the graft's architecture are in accordance with changes in bone density.

Functional cortical changes of the sensorimotor network are associated with clinical recovery in multiple sclerosis

To assess the early cortical changes following an acute motor relapse secondary to a pseudotumoral lesion in MS patients, the longitudinal cortical functional correlates of clinical recovery, and the evolution over time of cortical reorganization. FMRI during the performance of a simple motor task were obtained from 12 MS patients (after a clinical attack involving the motor system secondary to a pseudotumoral lesion) and 15 matched controls. In six patients and five controls, a longitudinal fMRI study was also performed. In patients, at baseline, the primary sensorimotor cortex (SMC) of the ipsilateral (contralesional) hemisphere was significantly more active during task performance with the impaired than the unimpaired hand. During task performance with the unimpaired hand, the ipsilateral cerebellum and several motor areas in the contralateral hemisphere were significantly more active. Pseudotumoral lesion volume was correlated with activation of the primary SMC bilaterally (r = -0.86 and -0.85) and the nine-hole peg test score with activation of the primary SMC of the affected hemisphere (r = 0.88). A recovery of function of the primary SMC of the affected hemisphere was found in the four patients with clinical improvement. In the two patients without clinical recovery, there was a persistent recruitment of the primary SMC of the unaffected hemisphere. Pseudotumoral MS lesions affecting the motor system can determine short-term cortical changes characterized by the recruitment of pathways in the unaffected hemisphere. The regain of function of motor areas of the affected hemisphere seems to be a critical factor for a favorable recovery.

La neuroimagen en la enfermedad de Alzheimer: perspectiva actual

Clinically, computerized tomography scanning and magnetic resonance imaging (MRI) are the neuroimaging techniques most frequently used in the work up of progressive cognitive impairment, in order to rule out tumors or other treatable etiologies. However, as we move closer to having more effective treatments for Alzheimer's disease (AD), we experience a greater need to use markers of early brain injury. Among them is neuroimaging. In this review we give some examples of the role of MRI and of functional MRI (fMRI) as markers of early brain changes.Regional metabolism, studied with positron emission tomography (PET) can also be used advantageously to depict early cortical changes in mild cognitive impairment (MCI) and even presymptomatic AD. SPECT, less expensive than PET, has a lower sensitivity, but has been extensively studied and using quantification methods can help even in MCI. Newer PET markers allow for the evaluation of activated microglia in vivo, as well as for the study of amyloid deposition in the brain and the activity of enzymes such as acetyl-cholinesterase.Future refinements in the neuroimaging techniques seem likely to help in the early diagnosis, evaluation of potential treatments and clarification of pathogenetic mechanisms in AD.