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Aging and Disease Jun 2024The progression of Parkinson's disease (PD) is often accompanied by cognitive decline. We had previously developed a brain age estimation program utilizing structural...
The progression of Parkinson's disease (PD) is often accompanied by cognitive decline. We had previously developed a brain age estimation program utilizing structural MRI data of 949 healthy individuals from publicly available sources. Structural MRI data of 244 PD patients who were cognitively normal at baseline was acquired from the Parkinson Progression Markers Initiative (PPMI). 192 of these showed stable normal cognitive function from baseline out to 5 years (PD-SNC), and the remaining 52 had unstable normal cognition and developed mild cognitive impairment within 5 years (PD-UNC). 105 healthy controls were also included in the analysis as a reference. First, we examined if there were any baseline differences in regional brain structure between PD-UNC and PD-SNC cohorts utilizing the three most widely used atrophy estimation pipelines, i.e., voxel-based morphometry (VBM), deformation-based morphometry and cortical thickness analyses. We then investigated if accelerated brain age estimation with our multivariate regressive machine learning algorithm was different across these groups (HC, PD-SNC, and PD-UNC). As per the VBM analysis, PD-UNC patients demonstrated a noticeable increase in GM volume in the posterior and anterior lobes of the cerebellum, sub-lobar, extra-nuclear, thalamus, and pulvinar regions when compared to PD-SNC at baseline. PD-UNC patients were observed to have significantly older brain age compared to both PD-SNC patients (p=0.009) and healthy controls (p<0.009). The increase in GM volume in the PD-UNC group could potentially indicate an inflammatory or neuronal hypertrophy response, which could serve as a biomarker for future cognitive decline among this population.
PubMed: 38913040
DOI: 10.14336/AD.2024.0323 -
Neuroradiology Jun 2024Canavan disease (CD) is a rare autosomal recessive neurodegenerative disorder caused by a deficiency of aspartoacylase A, an enzyme that degrades N-acetylaspartate...
INTRODUCTION
Canavan disease (CD) is a rare autosomal recessive neurodegenerative disorder caused by a deficiency of aspartoacylase A, an enzyme that degrades N-acetylaspartate (NAA). The disease is characterized by progressive white matter degeneration, leading to intellectual disability, seizures, and death. This retrospective study aims to describe the full spectrum of magnetic resonance imaging (MRI) findings in a large case series of CD patients.
MATERIALS AND METHODS
MRI findings in 18 patients with confirmed CD were investigated, and the full spectrum of brain abnormalities was compared with the existing literature to provide new insights regarding the brain MRI findings in these patients. All the cases were proven based on genetic study or NAA evaluation in urine or brain.
RESULTS
Imaging analysis showed involvement of the deep and subcortical white matter as well as the globus pallidus in all cases, with sparing of the putamen, caudate, and claustrum. The study provides updates on the imaging characteristics of CD and validates some underreported findings such as the involvement of the lateral thalamus with sparing of the pulvinar, involvement of the internal capsules and corpus callosum, and cystic formation during disease progression.
CONCLUSION
To our knowledge, this is one of the largest case series of patients with CD which includes a detailed description of the brain MRI findings. The study confirmed many of the previously reported MRI findings but also identified abnormalities that were previously rarely or not described. We speculate that areas of ongoing myelination are particularly vulnerable to changes in CD.
PubMed: 38880823
DOI: 10.1007/s00234-024-03388-x -
Research Square May 2024The brain's functional architecture is intricately shaped by causal connections between its cortical and subcortical structures. Here, we studied 27 participants with...
The brain's functional architecture is intricately shaped by causal connections between its cortical and subcortical structures. Here, we studied 27 participants with 4864 electrodes implanted across the anterior, mediodorsal, and pulvinar thalamic regions, and the cortex. Using data from electrical stimulation procedures and a data-driven approach informed by neurophysiological standards, we dissociated three unique spectral patterns generated by the perturbation of a given brain area. Among these, a novel waveform emerged, marked by delayed-onset slow oscillations in both ipsilateral and contralateral cortices following thalamic stimulations, suggesting a mechanism by which a thalamic site can influence bilateral cortical activity. Moreover, cortical stimulations evoked earlier signals in the thalamus than in other connected cortical areas suggesting that the thalamus receives a copy of signals before they are exchanged across the cortex. Our causal connectivity data can be used to inform biologically-inspired computational models of the functional architecture of the brain.
PubMed: 38853954
DOI: 10.21203/rs.3.rs-4366486/v1 -
Psychiatry Research Aug 2024The use of methamphetamine in the United States is increasing, contributing now to the "fourth wave" in the national opioid epidemic crisis. People who suffer from... (Review)
Review
The use of methamphetamine in the United States is increasing, contributing now to the "fourth wave" in the national opioid epidemic crisis. People who suffer from methamphetamine use disorder (MUD) have a higher risk of death. No pharmacological interventions are approved by the FDA and psychosocial interventions are only moderately effective. Transcranial Magnetic Stimulation (TMS) is a relatively novel FDA-cleared intervention for the treatment of Major Depressive Disorder (MDD) and other neuropsychiatric conditions. Several lines of research suggest that TMS could be useful for the treatment of addictive disorders, including MUD. We will review those published clinical trials that show potential effects on craving reduction of TMS when applied over the dorsolateral prefrontal cortex (DLPFC) also highlighting some limitations that affect their generalizability and applicability. We propose the use of the Koob and Volkow's neurocircuitry model of addiction as a frame to explain the brain effects of TMS in patients with MUD. We will finally discuss new venues that could lead to a more individualized and effective treatment of this complex disorder including the use of neuroimaging, the exploration of different areas of the brain such as the frontopolar cortex or the salience network and the use of biomarkers.
Topics: Humans; Transcranial Magnetic Stimulation; Amphetamine-Related Disorders; Methamphetamine; Dorsolateral Prefrontal Cortex; Craving; Behavior, Addictive
PubMed: 38852478
DOI: 10.1016/j.psychres.2024.115995 -
Scientific Reports Jun 2024The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect...
The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect symptoms, including an overt spatial saccade bias during free choices. However, it remains unclear whether disrupting the dorsal pulvinar during target selection that relies on a perceptual decision leads to a perceptual impairment or a more general spatial orienting and choice deficit. To address this question, we reversibly inactivated the unilateral dorsal pulvinar by injecting GABA-A agonist THIP while two macaque monkeys performed a color discrimination saccade task with varying perceptual difficulty. We used Signal Detection Theory and simulations to dissociate perceptual sensitivity (d-prime) and spatial selection bias (response criterion) effects. We expected a decrease in d-prime if dorsal pulvinar affects perceptual discrimination and a shift in response criterion if dorsal pulvinar is mainly involved in spatial orienting. After the inactivation, we observed response criterion shifts away from contralesional stimuli, especially when two competing stimuli in opposite hemifields were present. Notably, the d-prime and overall accuracy remained largely unaffected. Our results underline the critical contribution of the dorsal pulvinar to spatial orienting and action selection while showing it to be less important for visual perceptual discrimination.
Topics: Animals; Pulvinar; Saccades; Male; Space Perception; Visual Perception; Photic Stimulation; Macaca mulatta; Attention
PubMed: 38834578
DOI: 10.1038/s41598-024-62056-5 -
World Neurosurgery May 2024Geniculocalcarine fibers are thought to be exclusively ipsilateral. However, recent findings challenged this belief, revealing bilateral recruiting responses in...
BACKGROUND
Geniculocalcarine fibers are thought to be exclusively ipsilateral. However, recent findings challenged this belief, revealing bilateral recruiting responses in occipitotemporoparietal regions upon unilateral stimulation of the lateral geniculate nucleus (LGN) in humans. This raised the intriguing possibility of bilateral projections to primary visual areas (V1). This study sought to explore the hypothetical decussation of the geniculocalcarine tract.
METHODS
40 healthy individuals' 7T magnetic resonance images from the Human Connectome Project were examined. Employing MRtrix3 software with the constrained spherical deconvolution algorithm, scans were processed. LGN served as the seed region and contralateral regions of interest (splenium of the corpus callosum, posterior commissure, LGN, V1, pulvinar, and superior colliculus) were defined to reconstruct the hypothetical decussated fibers. Tractography included contralateral V1 as the target region in all segmentations, excluding ipsilateral V1 to eliminate fibers leading to or originating from this area. Additionally, a segmentation of the tract originating from LGN and projecting to the ipsilateral V1 was performed. Mean fraction anisotropy and mean diffusivity metrics were extracted from the density maps.
RESULTS
Observations revealed a substantial volume of decussated fibers between LGN and contralateral V1 via the splenium of the corpus callosum, albeit much smaller than ipsilateral fibers. The volume of ipsilateral fibers was similar in both sides. Left LGN-originating decussated fibers were more than double those originating from the right LGN. Tract segmentation to other regions of interests yielded no fibers.
CONCLUSIONS
This study suggests a partial decussation of the fibers between LGN and V1, likely constituting the geniculocalcarine tract.
PubMed: 38823444
DOI: 10.1016/j.wneu.2024.05.152 -
Neurological Sciences : Official... May 2024Epileptic seizures are frequently associated with liver dysfunction and alcoholism. Subacute encephalopathy with seizures in chronic alcoholics (SESA) is an...
The role of EEG and neuroimaging in the diagnosis of non-convulsive status epilepticus in Subacute Encephalopathy with Seizures in Alcoholics (SESA syndrome): a case report and overview of the literature.
Epileptic seizures are frequently associated with liver dysfunction and alcoholism. Subacute encephalopathy with seizures in chronic alcoholics (SESA) is an underrecognized condition with peculiar clinical, EEG and neuroradiological features.We report the case of a 58-year-old man with previous alcohol use disorder (AUD) and acute-on chronic liver failure on alcohol-related cirrhosis, referred for urgent Orthotopic Liver Transplantation evaluation. The patient presented with delirium, aphasia and progressive deterioration of consciousness leading to intensive care unit admission. EEG showed slow activity with superimposed lateralized periodic discharges (LPDs) over the left temporo-occipital regions and ictal discharges with focal motor phenomena, consistent with focal status epilepticus. Antiseizure treatment with lacosamide and levetiracetam was administered with progressive improvement of consciousness.Brain MRI disclosed T2/FLAIR areas of hyperintensity in the left pulvinar and T2/FLAIR hyperintensity with corresponding DWI hyperintensity in the left hippocampal cortex, suggestive of post/peri-ictal excitotoxic changes with anatomical correspondence to focal LPDs distribution. SWI demonstrated decreased prominence of cortical veins in the left temporo-occipital region consistent with increased venous blood oxygenation in compensatory hyperperfusion.In conclusion, SESA should be suspected in the differential diagnosis of patients with AUD presenting with focal neurological deficits, seizures and focal EEG abnormalities. In this context, EEG and brain MRI represent useful tools with both diagnostic and prognostic value.
PubMed: 38802690
DOI: 10.1007/s10072-024-07609-2 -
Movement Disorders Clinical Practice May 2024Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate.
BACKGROUND
Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate.
OBJECTIVE
To investigate brain networks associated with anxiety in CD.
METHODS
Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales.
RESULTS
Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05).
CONCLUSION
Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD.
PubMed: 38747154
DOI: 10.1002/mdc3.14070 -
Annals of Clinical and Translational... Jun 2024To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo...
OBJECTIVE
To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI.
METHODS
In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex.
RESULTS
Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes.
INTERPRETATION
Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.
Topics: Humans; Female; Male; Adult; Thalamus; Cross-Sectional Studies; Middle Aged; Multiple Sclerosis; Atrophy; White Matter; Diffusion Magnetic Resonance Imaging
PubMed: 38725151
DOI: 10.1002/acn3.52026 -
Brain Sciences Apr 2024The primary visual cortex (V1) is one of the most studied regions of the brain and is characterized by its specialized and laminated layer 4 in human and non-human... (Review)
Review
The primary visual cortex (V1) is one of the most studied regions of the brain and is characterized by its specialized and laminated layer 4 in human and non-human primates. However, studies aiming to harmonize the definition of the cortical layers and borders of V1 across rodents and primates are very limited. This article attempts to identify and harmonize the molecular markers and connectional patterns that can consistently link corresponding cortical layers of V1 and borders across mammalian species and ages. V1 in primates has at least two additional and unique layers (L3b2 and L3c) and two sublayers of layer 4 (L4a and L4b) compared to rodent V1. In all species examined, layers 4 and 3b of V1 receive strong inputs from the (dorsal) lateral geniculate nucleus, and V1 is mostly surrounded by the secondary visual cortex except for one location where V1 directly abuts area prostriata. The borders of primate V1 can also be clearly identified at mid-gestational ages using gene markers. In rodents, a novel posteromedial extension of V1 is identified, which expresses V1 marker genes and receives strong inputs from the lateral geniculate nucleus. This V1 extension was labeled as the posterior retrosplenial cortex and medial secondary visual cortex in the literature and brain atlases. Layer 6 of the rodent and primate V1 originates corticothalamic projections to the lateral geniculate, lateral dorsal, and reticular thalamic nuclei and the lateroposterior-pulvinar complex with topographic organization. Finally, the direct geniculo-extrastriate (particularly the strong geniculo-prostriata) projections are probably major contributors to blindsight after V1 lesions. Taken together, compared to rodents, primates, and humans, V1 has at least two unique middle layers, while other layers are comparable across species and display conserved molecular markers and similar connections with the visual thalamus with only subtle differences.
PubMed: 38672021
DOI: 10.3390/brainsci14040372