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Cureus May 2021Awake craniotomy with intraoperative neurophysiological language mapping (INLM) is an established procedure for patients undergoing surgery to resection tumors in the...
Awake craniotomy with intraoperative neurophysiological language mapping (INLM) is an established procedure for patients undergoing surgery to resection tumors in the language cortex area. INLM and continuous neurophysiological monitoring allow assessment of the language function, which is not possible under general anesthesia. INLM of the brain areas provides a helpful tool to the operating surgeon in reducing the risks associated with tumor resection in the motor and language cortex. We present a literature review and the technical method used for INLM by utilizing direct electrical cortical stimulation. We also report the usefulness of INLM for evaluation of the language function during resection of cortical tumors, epilepsy foci, and arteriovenous malformations (AVMs) located near language areas. First, the central sulcus is identified by sensory mapping, followed by the motor cortex's identification by direct electrical cortical stimulation (DECS). Neurological assessment of the patient is done by auditory and visual feedback. The patient is asked to repeat numbers, days, words, sentences, read words, and name pictures during cortical stimulation. DECS may cause a slurring or speech arrest. Electrocorticography (ECoG) is also performed during cortical stimulation to identify any after-discharges. Examination of the patient occurs immediately after surgery, and then 24 hours, one week, six months, and 12 months postoperatively. Bipolar DECS for motor mapping with ECoG can safely and reliably be utilized to identify essential language areas with minimizing permanent language deficits and maximizing the extent of tumor resection.
PubMed: 34123657
DOI: 10.7759/cureus.14960 -
Alzheimer's Research & Therapy Sep 2023Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer's disease (AD). Studies have reported strong associations between p-tau and tau-PET...
BACKGROUND
Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer's disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables.
METHODS
We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (C-PIB), tau-PET (F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years).
RESULTS
Plasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p < .001), especially in temporo-parietal and dorsolateral frontal cortices. Both higher p-tau217 and FTP-SUVR values were associated with younger age, female sex, and lower cortical volume, but not with APOE-ε4 carriership. PIB-PET Centiloids were weakly correlated with FTP-SUVR (r = 0.26, p = 0.02), but not with p-tau217 (r = 0.10, p = 0.36). Regional PET-plasma associations varied with amyloid burden, with p-tau217 being more strongly associated with tau-PET in temporal cortex among patients with moderate amyloid-PET burden, and with tau-PET in primary cortices among patients with high amyloid-PET burden. Higher p-tau217 and FTP-SUVR values were independently associated with lower MMSE scores cross-sectionally, while only baseline FTP-SUVR predicted longitudinal MMSE decline when both biomarkers were included in the same model.
CONCLUSION
Plasma p-tau217 and tau-PET are strongly correlated in amyloid-PET-positive patients with MCI or dementia due to AD, and they exhibited comparable patterns of associations with demographic variables and with markers of downstream neurodegeneration.
Topics: Humans; Female; Middle Aged; Aged; Male; Retrospective Studies; Amyloidogenic Proteins; Alzheimer Disease; Cognitive Dysfunction
PubMed: 37740209
DOI: 10.1186/s13195-023-01302-w -
Psychiatry Research. Neuroimaging Jan 2022Cortical thickness has been increasingly studied in the context of structural-brain-behavior associations, such as anxiety; however, the literature is scattered across... (Review)
Review
Cortical thickness has been increasingly studied in the context of structural-brain-behavior associations, such as anxiety; however, the literature is scattered across methods and research fields. This scoping review aims to summarize the available data concerning the association between cortical thickness and anxiety-related measures and identify the current research gaps. Searches were conducted in PubMed, PsycINFO/PsycARTICLES, Web of Science, OpenGrey and Networked Digital Library of Theses and Dissertations, and reference lists of key studies. Two researchers independently screened the abstracts and full-text reports according to the eligibility criteria, as well as extracted and charted the data. Quantitative and descriptive syntheses were conducted. The included publications (n = 18) reported cross-sectional studies, and 17 used surface-based approaches to estimate cortical thickness. Differences in regional cortical thickness were found to be associated with different anxiety-related measures/processes. Brain regions of interest include the medial orbitofrontal cortex, the ventromedial prefrontal cortex, the insula, the temporo-parietal areas, and the anterior cingulate cortex. However, caution should be warranted when interpreting the available results, as there is high variability in the field across anxiety-related measures, distinctive anxiety disorders, and data processing conditions and analysis. More research into this association is needed, to replicate and clarify existing findings.
Topics: Anxiety; Anxiety Disorders; Brain; Cerebral Cortex; Cross-Sectional Studies; Humans
PubMed: 34896960
DOI: 10.1016/j.pscychresns.2021.111423 -
Complex Psychiatry Sep 2022Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to...
INTRODUCTION
Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to several translations of novel disease susceptibility genes into drug targets and care. This however has not been the case for analyses where sample sizes are small, which suffer from multiple comparisons testing. The present study examined the statistical impact of combining a burden test methodology, PrediXcan, with a multimodel meta-analysis, cross phenotype association (CPASSOC).
METHODS
The analysis was conducted on 5 addiction traits: family alcoholism, cannabis craving, alcohol, nicotine, and cannabis dependence and 10 brain tissues: anterior cingulate cortex BA24, cerebellar hemisphere, cortex, hippocampus, nucleus accumbens basal ganglia, caudate basal ganglia, cerebellum, frontal cortex BA9, hypothalamus, and putamen basal ganglia. Our sample consisted of 1,640 participants from the University of California, San Francisco (UCSF) Family Alcoholism Study. Genotypes were obtained through low pass whole genome sequencing and the use of Thunder, a linkage disequilibrium variant caller.
RESULTS
The post-PrediXcan, gene-phenotype association without aggregation resulted in 2 significant results, and . Aggregating across phenotypes resulted no significant findings. Aggregating across tissues resulted in 15 significant and 5 suggestive associations: and ; , and respectively.
DISCUSSION
Given the relatively small size of the cohort, this multimodel approach was able to find over a dozen significant associations between predicted gene expression and addiction traits. Of our findings, 8 had prior associations with similar phenotypes through investigation of the GWAS Atlas. With the onset of improved transcriptome data, this approach should increase in efficacy.
PubMed: 36407771
DOI: 10.1159/000523748 -
Behavioural Brain Research Sep 2021Adaptive behaviour is under the potent control of environmental cues. Such cues can acquire value by virtue of their associations with outcomes of motivational... (Review)
Review
Adaptive behaviour is under the potent control of environmental cues. Such cues can acquire value by virtue of their associations with outcomes of motivational significance, be they appetitive or aversive. There are at least two ways through which an environmental cue can acquire value, through first-order and higher-order conditioning. In first-order conditioning, a neutral cue is directly paired with an outcome of motivational significance. In higher-order conditioning, a cue is indirectly associated with motivational events via a directly conditioned first-order stimulus. The present article reviews some of the associations that support learning in first- and higher-order conditioning, as well as the role of the BLA and the molecular mechanisms involved in these two types of learning.
Topics: Animals; Association Learning; Avoidance Learning; Basolateral Nuclear Complex; Behavior, Animal; Cerebral Cortex; Conditioning, Psychological; Motivation
PubMed: 34197867
DOI: 10.1016/j.bbr.2021.113435 -
Annals of Neurology Aug 2023VGF is proposed as a potential therapeutic target for Alzheimer's (AD) and other neurodegenerative conditions. The cell-type specific and, separately, peptide specific...
OBJECTIVE
VGF is proposed as a potential therapeutic target for Alzheimer's (AD) and other neurodegenerative conditions. The cell-type specific and, separately, peptide specific associations of VGF with pathologic and cognitive outcomes remain largely unknown. We leveraged gene expression and protein data from the human neocortex and investigated the VGF associations with common neuropathologies and late-life cognitive decline.
METHODS
Community-dwelling older adults were followed every year, died, and underwent brain autopsy. Cognitive decline was captured via annual cognitive testing. Common neurodegenerative and cerebrovascular conditions were assessed during neuropathologic evaluations. Bulk brain RNASeq and targeted proteomics analyses were conducted using frozen tissues from dorsolateral prefrontal cortex of 1,020 individuals. Cell-type specific gene expressions were quantified in a subsample (N = 424) following single nuclei RNASeq analysis from the same cortex.
RESULTS
The bulk brain VGF gene expression was primarily associated with AD and Lewy bodies. The VGF gene association with cognitive decline was in part accounted for by neuropathologies. Similar associations were observed for the VGF protein. Cell-type specific analyses revealed that, while VGF was differentially expressed in most major cell types in the cortex, its association with neuropathologies and cognitive decline was restricted to the neuronal cells. Further, the peptide fragments across the VGF polypeptide resembled each other in relation to neuropathologies and cognitive decline.
INTERPRETATION
Multiple pathways link VGF to cognitive health in older age, including neurodegeneration. The VGF gene functions primarily in neuronal cells and its protein associations with pathologic and cognitive outcomes do not map to a specific peptide. ANN NEUROL 2023;94:232-244.
Topics: Humans; Aged; Brain; Cognitive Dysfunction; Neuropathology; Nervous System Diseases; Cognition; Alzheimer Disease; Nerve Growth Factors
PubMed: 37177846
DOI: 10.1002/ana.26676 -
Journal of Affective Disorders Sep 2022Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological...
BACKGROUND
Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression.
METHOD
Individuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed.
RESULTS
Depression severity was negatively associated with rostral ACC thickness (B = -0.55, p = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, p = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies.
CONCLUSION
Overall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved.
Topics: Anxiety Disorders; Brain; Depression; Depressive Disorder, Major; Gyrus Cinguli; Humans
PubMed: 35760189
DOI: 10.1016/j.jad.2022.06.056 -
Neuron Aug 2019The paraventricular thalamus (PVT) is an interface for brain reward circuits, with input signals arising from structures, such as prefrontal cortex and hypothalamus,...
The paraventricular thalamus (PVT) is an interface for brain reward circuits, with input signals arising from structures, such as prefrontal cortex and hypothalamus, that are broadcast to downstream limbic targets. However, the precise synaptic connectivity, activity, and function of PVT circuitry for reward processing are unclear. Here, using in vivo two-photon calcium imaging, we find that PVT neurons projecting to the nucleus accumbens (PVT-NAc) develop inhibitory responses to reward-predictive cues coding for both cue-reward associative information and behavior. The multiplexed activity in PVT-NAc neurons is directed by opposing activity patterns in prefrontal and lateral hypothalamic afferent axons. Further, we find that prefrontal cue encoding may maintain accurate cue-reward processing, as optogenetic disruption of this encoding induced long-lasting effects on downstream PVT-NAc cue responses and behavioral cue discrimination. Together, these data reveal that PVT-NAc neurons act as an interface for reward processing by integrating relevant inputs to accurately inform reward-seeking behavior.
Topics: Animals; Association Learning; Conditioning, Classical; Craving; Cues; Glutamic Acid; Hypothalamic Area, Lateral; Mice; Midline Thalamic Nuclei; Neural Pathways; Neurons; Optogenetics; Patch-Clamp Techniques; Prefrontal Cortex; Reward; gamma-Aminobutyric Acid
PubMed: 31196673
DOI: 10.1016/j.neuron.2019.05.018 -
Scientific Reports May 2023Acute alcohol intake produces subjective intoxication (SI) and response (SR; e.g., valanced stimulation and sedation), which has important implications for...
Acute alcohol intake produces subjective intoxication (SI) and response (SR; e.g., valanced stimulation and sedation), which has important implications for alcohol-related risk. Individuals who experience less SI may be more likely to engage in risky behaviors while drinking. Gray matter morphometry in brain regions underlying cognitive and affective processes may help to inform individual differences in subjective intoxication and response. The subjective effects of alcohol vary between limbs of the blood alcohol concentration (BAC) curve (i.e., whether BAC is rising or falling; acute tolerance). We examined the relationship between gray matter density (GMD) and SI/SR as a function of BAC limb. Healthy social drinkers (N = 89; 55 women) completed an alcohol challenge paradigm (target BAC = 0.08 g/dL) and structural magnetic resonance imaging (MRI). Participants completed measures of SR and SI on ascending and descending BAC limbs. Association between GMD and SI/SR on each limb were assessed using whole-brain, voxel-wise general linear models. GMD estimates were extracted from significant clusters. Differences in association of GMD and SI/SR between limbs were assessed using hierarchical regression. Significant associations of SI with GMD on the ascending limb were observed in the cerebellum. A significant association between SR and GMD on the descending limb were observed in the pre-motor cortex (BA6) and cerebellum. We identified common and unique associations among cerebellum and pre-central gyrus structures with SI and SR between BAC limbs. Functional imaging studies may further clarify unique dimensions of subjective alcohol effects linked to the observed structural associations.
Topics: Humans; Female; Alcohol Drinking; Blood Alcohol Content; Gray Matter; Motor Cortex; Ethanol; Cerebellum
PubMed: 37147409
DOI: 10.1038/s41598-023-34546-5 -
The Journal of Neuroscience : the... Apr 2022From an associative perspective the acquisition of new goal-directed actions requires the encoding of specific action-outcome (AO) associations and, therefore,...
From an associative perspective the acquisition of new goal-directed actions requires the encoding of specific action-outcome (AO) associations and, therefore, sensitivity to the validity of an action as a predictor of a specific outcome relative to other events. Although competitive architectures have been proposed within associative learning theory to achieve this kind of identity-based selection, whether and how these architectures are implemented by the brain is still a matter of conjecture. To investigate this issue, we trained human participants to encode various AO associations while undergoing functional neuroimaging (fMRI). We then degraded one AO contingency by increasing the probability of the outcome in the absence of its associated action while keeping other AO contingencies intact. We found that this treatment selectively reduced performance of the degraded action. Furthermore, when a signal predicted the unpaired outcome, performance of the action was restored, suggesting that the degradation effect reflects competition between the action and the context for prediction of the specific outcome. We used a Kalman filter to model the contribution of different causal variables to AO learning and found that activity in the medial prefrontal cortex (mPFC) and the dorsal anterior cingulate cortex (dACC) tracked changes in the association of the action and context, respectively, with regard to the specific outcome. Furthermore, we found the mPFC participated in a network with the striatum and posterior parietal cortex to segregate the influence of the various competing predictors to establish specific AO associations. Humans and other animals learn the consequences of their actions, allowing them to control their environment in a goal-directed manner. Nevertheless, it is unknown how we parse environmental causes from the effects of our own actions to establish these specific action-outcome (AO) relationships. Here, we show that the brain learns the causal structure of the environment by segregating the unique influence of actions from other causes in the medial prefrontal and anterior cingulate cortices and, through a network of structures, including the caudate nucleus and posterior parietal cortex, establishes the distinct causal relationships from which specific AO associations are formed.
Topics: Animals; Corpus Striatum; Gyrus Cinguli; Humans; Learning; Magnetic Resonance Imaging; Parietal Lobe; Prefrontal Cortex; Problem-Based Learning
PubMed: 35296548
DOI: 10.1523/JNEUROSCI.1079-21.2022