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Journal of Affective Disorders Jun 2024Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression... (Review)
Review
BACKGROUND
Previous task-related functional magnetic resonance imaging (task-fMRI) investigations have documented abnormal brain activation associated with subclinical depression (SD), defined as a clinically relevant level of depressive symptoms that does not meet the diagnostic criteria for major depressive disorder. However, these task-fMRI studies have not reported consistent conclusions. Performing a voxel-based meta-analysis of task-fMRI studies may yield reliable findings.
METHODS
We extracted the peak coordinates and t values of included studies and analyzed brain activation between individuals with SD and healthy controls (HCs) using anisotropic effect-size signed differential mapping (AES-SDM).
RESULTS
A systematic literature search identified eight studies, including 266 individuals with SD and 281 HCs (aged 14 to 25). The meta-analysis showed that individuals with SD exhibited significantly greater activation in the right lenticular nucleus and putamen according to task-fMRI. The meta-regression analysis revealed a negative correlation between the proportion of females in a group and activation in the right striatum.
LIMITATIONS
The recruitment criteria for individuals with SD, type of tasks and MRI acquisition parameters of included studies were heterogeneous. The results should be interpreted cautiously due to insufficient included studies.
CONCLUSION
Our findings suggest that individuals with SD exhibit increased activation in the right lenticular nucleus, putamen and striatum, which may indicate a compensatory increase in response to an impairment of insular and striatal function caused by depression. These results provide valuable insights into the potential pathophysiology of brain dysfunction in SD.
PubMed: 38909758
DOI: 10.1016/j.jad.2024.06.040 -
Frontiers in Psychiatry 2024Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a...
INTRODUCTION
Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt.
METHODS
We examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (M [SD] = 16.4[0.3], 41% male) and 13 with AT (M [SD] = 16.2[0.3], 31% male).
RESULTS
Only the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise <.001, cluster-wise <.01). No significant associations were found between any putamen RSFC patterns and suicidal ideation severity or lethality of attempts among those who had attempted.
DISCUSSION
The results align with recent adult literature and have interesting theoretical and clinical implications. A possible interpretation of the results is a mismatch of the serotonin transport to putamen and to the supplementary motor area and the resulting reduced functional connectivity between the two areas in adolescents with attempt history. The obtained results can be used to enhance the diathesis-stress model and the Emotional paiN and social Disconnect (END) model of adolescent suicidality by adding the putamen. We also speculate that connectivity between putamen and the supplementary motor area may in the future be used as a valuable biomarker of treatment efficacy and possibly prediction of treatment outcome.
PubMed: 38903634
DOI: 10.3389/fpsyt.2024.1364271 -
Frontiers in Neuroscience 2024VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms,...
VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.
PubMed: 38903599
DOI: 10.3389/fnins.2024.1394478 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2024Lead poisoning in childhood remains an important public health concern. We highlight the radiological findings in a patient with a high blood lead concentration.
INTRODUCTION
Lead poisoning in childhood remains an important public health concern. We highlight the radiological findings in a patient with a high blood lead concentration.
CASE SUMMARY
A 7-year-old girl presented to hospital with abdominal pain, nausea, and asthenia. Laboratory tests showed severe hypochromic microcytic anemia, punctate basophilic stippling of erythrocytes, and a blood lead concentration of 880 µg/L (4.3 µmol/L).
IMAGES
Radiographs of the femur, tibia, and fibula demonstrated dense metaphyseal bands ("lead lines"). On cranial computed tomography, we observed multiple speck-like and curvilinear hyperdensities involving subcortical regions, putamen, and left cerebellar hemisphere.
CONCLUSION
In patients with lead poisoning, imaging of the brain and bones may show characteristic features. These imaging findings may point to the diagnosis of lead toxicity when these radiographic findings are discovered during the evaluation of vague complaints such as abdominal pain or mental status changes or when a blood lead concentration is not readily available.
PubMed: 38899783
DOI: 10.1080/15563650.2024.2342928 -
Journal of Affective Disorders Jun 2024While it is well-established that humans possess an innate need for social belonging, the neural mechanisms underlying motivation for connection are still largely...
BACKGROUND
While it is well-established that humans possess an innate need for social belonging, the neural mechanisms underlying motivation for connection are still largely unknown. We propose that inclusion motivation - measured through the effort that individuals are willing to invest to be included in social interactions - may serve as one of the basic building blocks of social behavior and may change in lonely individuals.
METHODS
Following the screening of 303 participants, we scanned 30 low- and 28 high-loneliness individuals with functional magnetic resonance imaging while they performed the Active Inclusion Task (AIT). The AIT assesses the participants' levels of effort invested in influencing their inclusion during classic Cyberball conditions of fair play and exclusion.
RESULTS
High- compared to low-loneliness individuals showed higher urgency for inclusion, specifically during fair play, which correlated with higher activity in the right thalamus. Furthermore, in high-loneliness individuals, we found increased functional connectivity between the thalamus and the temporoparietal junction, putamen, and insula.
LIMITATIONS
Participants interacted with computerized avatars, reducing ecological validity. Additionally, although increasing inclusion in the task required action, the physical demand was not high. Additional limitations are discussed.
CONCLUSIONS
Inclusion motivation in loneliness is heightened during fair but not exclusionary interactions, and is linked to activity in brain regions implicated in appetitive behavior and social cognition. The findings indicate that lonely individuals may view threat in inclusionary interactions, prompting them to take action to regain connection. This suggests that inclusion motivation may help explain social difficulties in loneliness.
PubMed: 38897307
DOI: 10.1016/j.jad.2024.06.049 -
Investigative Radiology Jun 2024The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences...
OBJECTIVES
The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences depends on the image resolution.
MATERIALS AND METHODS
Ultrahigh resolution (UHR) 3D MP2RAGE (magnetization-prepared 2 rapid acquisition gradient echo) T1-weighted MR images (voxel size, 0.7 × 0.7 × 0.7 mm3) of the brain of 30 subjects (18 women and 12 men; mean age, 39.0 ± 14.8 years) without abnormal findings on MRI were retrospectively included. MRI was performed on a whole-body 7 T MR system. A convolutional neural network was used to segment the following structures: frontal cortex, frontal white matter, thalamus, putamen, globus pallidus, caudate nucleus, and corpus callosum. Eighty-seven radiomic features were extracted respectively: gray-level histogram (n = 18), co-occurrence matrix (n = 24), run-length matrix (n = 16), size-zone matrix (n = 16), and dependence matrix (n = 13). Feature extraction was performed at UHR and, additionally, also after resampling to 1.4 × 1.4 × 1.4 mm3 voxel size (standard clinical resolution). Principal components (PCs) of radiomic features were calculated, and independent samples t tests with Cohen d as effect size measure were used to assess differences in PCs between women and men for the different cerebral structures.
RESULTS
At UHR, at least a single PC differed significantly between women and men in 6/7 cerebral structures: frontal cortex (d = -0.79, P = 0.042 and d = -1.01, P = 0.010), frontal white matter (d = -0.81, P = 0.039), thalamus (d = 1.43, P < 0.001), globus pallidus (d = 0.92, P = 0.020), caudate nucleus (d = -0.83, P = 0.039), and corpus callosum (d = -0.97, P = 0.039). At standard clinical resolution, only a single PC extracted from the corpus callosum differed between sexes (d = 1.05, P = 0.009).
CONCLUSIONS
Nonnegligible differences in radiomic features of several key structures of the brain exist between women and men, and need to be accounted for. Very high spatial resolution may be required to uncover and further investigate the sexual dimorphism of brain structures on MRI.
PubMed: 38896439
DOI: 10.1097/RLI.0000000000001088 -
General Psychiatry 2024Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains...
BACKGROUND
Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains limited.
AIMS
This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD.
METHODS
This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction.
RESULTS
Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p<0.001, uncorrected, with cluster level above 50 contiguous voxels). The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus (R=0.1690, p=0.030), left parahippocampal gyrus (R=0.1464, p=0.045) and left putamen (R=0.1967, p=0.018) in patients with OCD.
CONCLUSIONS
Adults with OCD demonstrated lower F-labelled difluoro analogue of F-SynVesT-1 compared with HCs, indicating potentially lower synaptic density. This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.
PubMed: 38894874
DOI: 10.1136/gpsych-2023-101208 -
CNS Neuroscience & Therapeutics Jun 2024The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering...
AIMS
The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering higher level of consciousness compared to patients with the unresponsive wakefulness syndrome (UWS). However, differentiation of the MCS and UWS poses challenge in clinical practice. This study aimed to explore glucose metabolic pattern (GMP) obtained from F-labeled-fluorodeoxyglucose positron emission tomography (F-FDG-PET) in distinguishing between UWS and MCS.
METHODS
Fifty-seven patients with disorders of consciousness (21 cases of UWS and 36 cases of MCS) who had undergone repeated standardized Coma Recovery Scale-Revised (CRS-R) evaluations were enrolled in this prospective study. F-FDG-PET was carried out in all patients and healthy controls (HCs). Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate GMPs. The expression score of whole-brain GMP was obtained, and its diagnostic accuracy was compared with the standardized uptake value ratio (SUVR). The diagnostic efficiency was validated by one-year later clinical outcomes.
RESULTS
UWS-MCS GMP exhibited hypometabolism in the frontal-parietal cortex, along with hypermetabolism in the unilateral lentiform nucleus, putamen, and anterior cingulate gyrus. The UWS-MCS-GMP expression score was significantly higher in UWS compared to MCS patients (0.90 ± 0.85 vs. 0 ± 0.93, p < 0.001). UWS-MCS-GMP expression score achieved an area under the curve (AUC) of 0.77 to distinguish MCS from UWS, surpassing that of SUVR based on the frontoparietal cortex (AUC = 0.623). UWS-MCS-GMP expression score was significantly correlated with the CRS-R score (r = -0.45, p = 0.004) and accurately predicted the one-year outcome in 73.7% of patients.
CONCLUSION
UWS and MCS exhibit specific glucose metabolism patterns, the UWS-MCS-GMP expression score significantly distinguishes MCS from UWS, making SSM/PCA a potential diagnostic methods in clinical practice for individual patients.
Topics: Humans; Female; Male; Middle Aged; Adult; Glucose; Fluorodeoxyglucose F18; Brain; Positron-Emission Tomography; Persistent Vegetative State; Aged; Prospective Studies; Young Adult
PubMed: 38894559
DOI: 10.1111/cns.14787 -
Neurology Jul 2024Cognitive impairment is a frequent nonmotor symptom in patients with Parkinson disease (PD), and early cognitive decline is often attributed to dopaminergic system...
BACKGROUND AND OBJECTIVES
Cognitive impairment is a frequent nonmotor symptom in patients with Parkinson disease (PD), and early cognitive decline is often attributed to dopaminergic system dysfunction. We aimed to explore spatiotemporal progression patterns of striatal dopamine availability and regional brain volume based on cognitive status among patients with PD.
METHODS
This retrospective, cross-sectional study included patients with newly diagnosed PD who were not taking medication for this condition who visited a university-affiliated hospital in Seoul between January 2018 and December 2020. Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or PD dementia (PDD) based on Seoul Neuropsychological Screening Battery-II, which includes 31 subsets covering activities of daily living and 5 cognitive domains. They all had brain imaging with MRI and PET with F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane at baseline. Subsequently, standardized uptake value ratios (SUVRs) for regional dopamine availability and regional gray matter volumes were obtained using automated segmentation. These metrics were compared across cognitive status groups, and spatiotemporal progression patterns were analyzed using the Subtype and Stage Inference machine learning technique.
RESULTS
Among 168 patients (mean age, 73.3 ± 6.1 years; 81 [48.2%] women), 65 had PD-NC, 65 had PD-MCI, and 38 had PDD. Patients with PD-MCI exhibited lower SUVRs (3.61 ± 1.31, < 0.001) in the caudate than patients with PD-NC (4.43 ± 1.21) but higher SUVRs than patients with PDD (2.39 ± 1.06). Patients with PD-NC had higher thalamic SUVRs (1.55 ± 0.16, < 0.001) than patients with both PD-MCI (1.45 ± 0.16) and PDD (1.38 ± 0.19). Regional deep gray matter volumes of the caudate ( = 0.015), putamen ( = 0.012), globus pallidus ( < 0.001), thalamus ( < 0.001), hippocampus ( < 0.001), and amygdala ( < 0.001) were more reduced in patients with PD-MCI or PDD than in patients with PD-NC, and the SUVR of the caudate correlated with caudate volume ( = 0.187, = 0.015). Hippocampal atrophy was the initial change influencing cognitive impairment. The reduced dopamine availability of the thalamus preceded reductions in volume across most deep gray matter regions.
DISCUSSION
Our finding underscores the association between decreased dopamine availability and volume of the caudate and thalamus with cognitive dysfunction in PD. The dopamine availability of the caudate and thalamus was reduced before the volume of the caudate and thalamus was decreased, highlighting the spatiotemporal association between dopaminergic and structural pathology in cognitive impairment in PD.
Topics: Humans; Parkinson Disease; Male; Female; Gray Matter; Cognitive Dysfunction; Aged; Cross-Sectional Studies; Retrospective Studies; Disease Progression; Middle Aged; Dopamine; Positron-Emission Tomography; Magnetic Resonance Imaging
PubMed: 38885485
DOI: 10.1212/WNL.0000000000209498 -
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