Parahippocampal Gyrus Research Articles

Magnitude and kinetics of a set of neuroanatomic volume and thickness together with white matter hyperintensity is definitive of cognitive status and brain age

Even among the subjects classified as cognitively normal, there exists a subset of individuals at a given chronological age (CA) who harbor white matter hyperintensity (WMH) while another subset presents with low or undetectable WMH. Here, we conducted a comprehensive MRI segmentation of neuroanatomic structures along with WMH quantification in groups of cognitively normal (CN), cognitively impaired (CI) individuals, and individuals with an etiological diagnosis of cognitive impairment owing to Alzheimer’s Disease (CI-AD) across the early (50–64 years), intermediate (65–79 years), and late (≥80 years) age groups from the NACC cohort. Neuroanatomic volumetry quantification revealed that thinning of the parahippocampal gyrus in the early (p = 0.016) and intermediate age groups (p = 0.0001) along with an increase in CSF (p = 0.0009) delineates between CI and CI-AD subjects. Although, a significant loss of ~5–10% in volume of gray matter (p(CN vs CI) < 0.0001, p(CN vs CI-AD) < 0.0001), white matter (p(CN vs CI) = 0.002, p(CN vs CI-AD) = 0.0003) and hippocampus (p(CN vs CI) = 0.007, p(CN vs CI-AD) < 0.0001) was evident at the early age groups in the CI and CI-AD compared to CN but it was not distinct between CI and CI-AD. Using the neuroanatomic and WMH volume, and the supervised decision tree-based ML modeling, we have established that a minimum set of Three brain quantities; Total brain (GM + WM), CSF, and WMH volume, provide the Optimal quantitative features discriminative of cognitive status as CN, CI, and CI-AD. Furthermore, using the volume/thickness of 178 neuroanatomic structures, periventricular and deep WMH volume quantification for the 819 CN subjects, we have developed a quantitative index as ‘Brain Age’ (BA) depictive of neuroanatomic health at a given CA. Subjects with elevated WMH load (5–10 ml) had increased BA ( + 0.6 to +4 years) than the CA. Increased BA in the subjects with elevated WMH is suggestive of WMH-induced vascular insult leading to accelerated and early structural loss than expected for a given CA. Henceforth, this study establishes that quantification of WMH together with an optimal number of neuroanatomic features is mandatory to delve into the biological underpinning of aging and aging-associated cognitive disorders.

Plasma metabolomic signature of healthy lifestyle, structural brain reserve and risk of dementia.

Although the association between healthy lifestyle and dementia risk has been documented, the relationship between a metabolic signature indicative of healthy lifestyle and dementia risk and the mediating role of structural brain impairment remain unknown. We retrieved 136 628 dementia-free participants from UK Biobank. Elastic net regression was used to obtain a metabolic signature that represented lifestyle behaviours. Cox proportional hazard models were fitted to explore the associations of lifestyle-associated metabolic signature with incident dementia. Causal associations between identified metabolites and dementia were investigated using Mendelian randomization. Mediation analysis was also conducted to uncover the potential mechanisms involving 19 imaging-derived phenotypes (brain volume, grey matter volume, white matter volume and regional grey matter volumes). During a follow-up of 12.55 years, 1783 incident cases of all-cause dementia were identified, including 725 cases of Alzheimer's dementia and 418 cases of vascular dementia. We identified 83 metabolites that could represent healthy lifestyle behaviours using elastic net regression. The metabolic signature was associated with a lower dementia risk, and for each standard deviation increment in metabolic signature, the hazard ratio was 0.89 [95% confidence interval (CI): 0.85, 0.93] for all-cause dementia, 0.95 (95% CI: 0.88, 1.03) for Alzheimer's dementia and 0.84 (95% CI: 0.77, 0.91) for vascular dementia. Mendelian randomization revealed potential causal associations between the identified metabolites and risk of dementia. In addition, the specific structural brain reserve, including the hippocampus, grey matter in the hippocampus, parahippocampal gyrus and middle temporal gyrus, were detected to mediate the effects of metabolic signature on dementia risk (mediated proportion ranging from 6.21% to 11.98%). The metabolic signature associated with a healthy lifestyle is inversely associated with dementia risk, and greater structural brain reserve plays an important role in mediating this relationship. These findings have significant implications for understanding the intricate connections between lifestyle, metabolism and brain health.

Disrupted brain functional asymmetry at rest in patients with major depressive disorder associated with sleep disturbances.

Sleep disturbances (SD) are common in major depressive disorder (MDD) patients. Brain functional asymmetry is crucial for understanding MDD pathophysiology. Previous studies using the parameter of asymmetry (PAS) approach have found brain functional asymmetry disruption in MDD. However, this has not been explored in MDD patients with SD. This study examined 26 MDD patients with SD, 34 MDD patients without SD, and 34 healthy controls using resting-state functional magnetic resonance imaging scans. SD symptoms were quantified using the 17-item Hamilton Rating Scale for Depression. PAS approach was used to evaluate functional asymmetry. MDD patients with SD displayed increased PAS in the left middle frontal gyrus (MFG)/inferior frontal gyrus (IFG) and decreased PAS in the left parahippocampal gyrus (PHG) compared to MDD patients without SD. Increased PAS in the left MFG/IFG was positively correlated with SD severity, and a negative correlation was found between decreased PAS in the left PHG and SD scores in all MDD patients. Receiver operating characteristic analysis indicated that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may serve as potential neuroimaging markers to differentiate MDD patients with SD from those without SD with Area Under Curve values of 0.8157 and 0.8068, respectively. These results highlighted that increased PAS in the left MFG/IFG and decreased PAS in the left PHG may be considered a prominent feature associated with SD symptoms of MDD patients, potentially serving as imaging markers to discriminate between MDD patients with and without SD.

Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

A - 1 Informant Report of Practical Judgment Is Associated with Mild Cognitive Impairment and Measures of Brain Structure in a Nondemented Sample of Older Adults

Abstract Objective Given the potential risks associated with compromised judgment in older adulthood, we examined whether informant-reported practical judgment abilities were associated with cognitive impairment and measures of brain structure. Method 97 community-dwelling older adults with informants (Mage = 74.64 ± 7.42, Medu = 15.76 ± 2.42, 74%female, 92%white) underwent neuropsychological evaluation, including the Test of Practical Judgment-Informant (TOP-J-INF), a 15-item informant-reported scale of judgment ability. Participants were diagnosed with mild cognitive impairment (MCI; n = 33) or as neuropsychologically unimpaired (n = 64). Participants completed an MRI study including T1-weighted image processed with FreeSurfer software (v 6.0.0) to obtain estimates of gray matter volume and cortical thickness (parcellated with the Desikan-Killiany atlas). Logistic and linear models analyzed the association of TOP-J-INF with MCI diagnosis and brain volume/thickness (in separate models). To better support the exploratory nature of this analysis of associations with structural brain variables, we did not apply correction for multiple comparisons. Results Each additional point on the TOP-J-INF increased the odds of MCI diagnosis by 16.8% (OR = 1.168, p = 0.004). Worse judgment was associated with reduced brain volume in the right parahippocampal gyrus (β = −11.688, p = 0.032), superior temporal gyrus (β = −51.330, p = 0.040), rostral anterior cingulate cortex (β = −25.704, p = 0.004); and reduced thickness of the left transverse temporal gyrus (β = −0.010, p = 0.041). Conclusions To our knowledge, this is the first study to investigate the relationship between informant report of judgment and measures of brain structure, providing support that informant concerns about a loved one’s compromised judgment is associated with volume/thickness reduction in key brain regions. Assessing practical judgment abilities via informants could provide critical clinical information when working with vulnerable older individuals.

Neural basis of false recognition in Alzheimer's disease and dementia with lewy bodies.

In Alzheimer's disease (AD), reports on the association between false recognition and brain structure have been inconsistent. In dementia with Lewy bodies (DLB), no such association has been reported. This study aimed to identify brain regions associated with false recognition in AD and DLB by analyzing regional gray matter volume (rGMV). We included 184 patients with AD and 60 patients with DLB. The number of false recognitions was assessed using the Alzheimer's Disease Assessment Scale' word recognition task. Brain regions associated with the number of false recognitions were examined by voxel-based morphometry analysis. The number of false recognitions significantly negatively correlated with rGMV in the bilateral hippocampus, left parahippocampal gyrus, bilateral amygdala, and bilateral entorhinal cortex in patients with AD (p < 0.05, family-wise error [FEW] corrected) and in the bilateral hippocampus, left parahippocampal gyrus, right inferior frontal gyrus, right middle frontal gyrus, right basal forebrain, right insula, left medial and lateral orbital gyri, and left fusiform in those with DLB (p < 0.05, FWE corrected). Bilateral hippocampus and left parahippocampal gyrus were associated with false recognition in both diseases. However, we found there were regions where the association between false recognition and rGMV differed from disease to disease.

Limbic Network Derangement Mediates Unawareness of Apathy in Mild Cognitive Impairment due to Alzheimer's Disease: Clues from [18F]FDG PET Voxel-Wise Analysis.

Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.

Teaching Video NeuroImage: Ictal Whistling Associated With Dominant Parahippocampal Gyrus Cortical Dysplasia.

Teaching Video NeuroImage: Ictal Whistling Associated With Dominant Parahippocampal Gyrus Cortical Dysplasia.

Electroencephalography-based endogenous phenotype of diagnostic transition from major depressive disorder to bipolar disorder

The neuropathology of mood disorders, including the diagnostic transition from major depressive disorder (MDD) to bipolar disorder (BD), is poorly understood. This study investigated resting-state electroencephalography (EEG) activity in patients with MDD and those whose diagnosis changed from MDD to BD. Among sixty-eight enrolled patients with MDD, the diagnosis of 17 patients converted to BD during the study period. We applied machine learning techniques to differentiate the two groups using sensor- and source-level EEG features. At the sensor level, patients with BD showed higher theta band power at the AF3 channel and low-alpha band power at the FC5 channel compared to patients with MDD. At the source level, patients with BD showed higher theta band activity in the right anterior cingulate and low-alpha band activity in the left parahippocampal gyrus. These four EEG features were selected for discriminating between BD and MDD with the best classification performance showing an accuracy of 80.88%, a sensitivity of 76.47%, and a specificity of 82.35%. Our findings revealed distinct theta and low-alpha band activities in patients with BD and MDD. These differences could potentially serve as candidate neuromarkers for the diagnosis and diagnostic transition between the two distinct mood disorders.

Hippocampal volume maximally modulates the relationship between subsyndromal symptomatic depression and cognitive impairment in non-demented older adults

BackgroundSubsyndromal symptomatic depression (SSD) is associated with an elevated risk of cognitive impairment in non-demented older adults. Given that hippocampal and middle temporal gyrus atrophy have been shown to cause SSD, our study aimed to investigate the effect of hippocampal volume on the association between SSD and cognitive impairment. Methods338 non-demented older adults from the ADNI (Alzheimer's Disease Neuroimaging Initiative) cohort who underwent cognitive assessments, questionnaires on depressive symptoms and MRI brain were studied. SSD group is defined as a score of 1–5 based on Geriatric Depression Scale scores. We conducted causal mediation analyses to investigate the effect of hippocampal volume on cognitive performance cross-sectionally. ResultsThe SSD group displayed lower left and right hippocampal volume (p<0.01) than the non-SSD group. SSD was linked to poorer cognition and smaller hippocampal volume. We found that hippocampal volume partially mediated the effect of SSD on cognitive performance including the global cognition and the cognitive section of Alzheimer's Disease Assessment Scale, with mediation percentages ranging from 6.45 % to 30.46 %. In addition, we found that the thickness of the left middle temporal, right entorhinal and right fusiform gyrus, brain regions linked to AD, mediate the relationship between SSD and cognition with mediation percentages ranging from 8.67 % to 21.44 %. LimitationsOur article didn't differentiate between mild cognitive impairment and normal population. ConclusionThe associations of SSD and cognitive impairment are linked to alterations in Alzheimer's Disease related brain regions.

Differences in subcortical functional connectivity in patients with epilepsy.

Epilepsy is a disease characterized by abnormal paroxysmal bioelectrical activity in the brain cortex and subcortical structures. Seizures per se change brain metabolism in epileptic focus and in distal parts of the brain. However, interictal phenomena can also affect functional connectivity (FC) and brain metabolism in other parts of the brain. We hypothesised that epilepsy affects functional connectivity not only among cortical, but also between subcortical, structures of the brain in a resting state condition. Investigating functional connectivity in patients with epilepsy could provide insights into the underlying pathophysiological mechanisms. Better understanding may lead to more effective treatment strategies. Functional connectivity was analysed in 35 patients with epilepsy and in 28 healthy volunteers. The group of patients was divided into generalised and focal epilepsy (temporal and extratemporal subgroups). Each patient and healthy volunteer underwent an fMRI resting-state session. During the study, EEG signals were simultaneously recorded with fMRI to facilitate the subsequent detection of potential interictal epileptiform discharges (IEDs). Their potential impact on BOLD signals was mitigated through linear regression. The data was processed and correlation coefficients (FC values) between the BOLD signal from selected structures of the central nervous system were determined and compared between study groups. The results were presented as significant differences in correlation coefficients between brain/subcortical structures in the epilepsy and control groups. Lower FC values for the epilepsy group compared to the control group were shown for connections related to the MPFC, hippocampus, thalamus, amygdala, and the parahippocampal gyrus. Epilepsy alters the functional connectivity of resting state subcortical networks. Patterns of pathological changes of FC differ between epilepsy subtypes, with predominant lower FC between the hippocampus, parahippocampal gyrus, amygdala and thalamus in patients with epilepsy. This study suggests that epilepsy affects subcortical structures. Identifying distinct patterns of altered FC in epilepsy subtypes may help to tailor treatment strategies. Changes in FC detected by fMRI may precede clinical symptoms, aiding in the early diagnosis of cognitive and emotional disorders in focal epilepsy.

Neural substrate for the engagement of the ventral visual stream in motor control in the macaque monkey.

The present study aimed to describe the cortical connectivity of a sector located in the ventral bank of the superior temporal sulcus in the macaque (intermediate area TEa and TEm [TEa/m]), which appears to represent the major source of output of the ventral visual stream outside the temporal lobe. The retrograde tracer wheat germ agglutinin was injected in the intermediate TEa/m in four macaque monkeys. The results showed that 58-78% of labeled cells were located within ventral visual stream areas other than the TE complex. Outside the ventral visual stream, there were connections with the memory-related medial temporal area 36 and the parahippocampal cortex, orbitofrontal areas involved in encoding subjective values of stimuli for action selection, and eye- or hand-movement related parietal (LIP, AIP, and SII), prefrontal (12r, 45A, and 45B) areas, and a hand-related dysgranular insula field. Altogether these data provide a solid substrate for the engagement of the ventral visual stream in large scale cortical networks for skeletomotor or oculomotor control. Accordingly, the role of the ventral visual stream could go beyond pure perceptual processes and could be also finalized to the neural mechanisms underlying the control of voluntary motor behavior.

Disrupted cognitive network revealed by task-induced brain entropy in schizophrenia.

Brain entropy (BEN), which measures the amount of information in brain activity, provides a novel perspective for evaluating brain function. Recent studies using resting-state functional magnetic resonance imaging (fMRI) have shown that BEN during rest can help characterize brain function alterations in schizophrenia (SCZ). However, there is a lack of research on BEN using task-evoked fMRI to explore task-dependent cognitive deficits in SCZ. In this study, we evaluate whether the reduced working memory (WM) capacity in SCZ is possibly associated with dynamic changes in task BEN during tasks with high cognitive demands. We analyzed data from 15 patients with SCZ and 15 healthy controls (HC), calculating task BEN from their N-back task fMRI scans. We then examined correlations between task BEN values, clinical symptoms, 2-back task performance, and neuropsychological test scores. Patients with SCZ exhibited significantly reduced task BEN in the cerebellum, hippocampus, parahippocampal gyrus, thalamus, and the middle and superior frontal gyrus (MFG and SFG) compared to HC. In HC, significant positive correlations were observed between task BEN and 2-back accuracy in several brain regions, including the MFG and SFG; such correlations were absent in patients with SCZ. Additionally, task BEN was negatively associated with scores for both positive and negative symptoms in areas including the parahippocampal gyrus among patients with SCZ. In conclusion, our findings indicate that a reduction in BEN within prefrontal and hippocampal regions during cognitively demanding tasks may serve as a neuroimaging marker for SCZ.

Age differences in functional connectivity track dedifferentiation of category representations.

With advancing age, the distinctiveness of neural representations of information declines. While the finding of this so-called 'age-related neural dedifferentiation' in category-selective neural regions is well-described, the contribution of age-related changes in network organization to dedifferentiation is unknown. Here, we asked whether age differences in a) whole-brain network segregation (i.e., network dedifferentiation) and b) functional connectivity to category-selective neural regions are related to regional dedifferentiation of categorical representations. Younger and older adults viewed blocks of face and house stimuli in the fMRI scanner. We found an age-related decline in neural distinctiveness for faces in the fusiform gyrus (FG) and for houses in the parahippocampal gyrus (PHG). Functional connectivity analyses revealed age-related dedifferentiation of global network structure as well as age differences in connectivity between the FG and early visual cortices. Interindividual correlations demonstrated that regional distinctiveness was related to network segregation. Together, our findings suggest that dedifferentiation of categorical representations may be linked to age-related reorganization of functional networks.

Causal relationships of grey matter structures in multiple sclerosis and neuromyelitis optica spectrum disorder: insights from Mendelian randomization.

Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus (β = 0.018, P = 2.383 × 10-4) and negatively associated with the volumes of the bilateral caudate (left: β = -0.020, P = 7.203 × 10-5; right: β = -0.021, P = 3.274 × 10-5) and putamen nuclei (left: β = -0.030, P = 2.175 × 10-8; right: β = -0.024, P = 1.047 × 10-5). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus (β = 0.023, P = 1.025 × 10-4). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.

Quantitative assessment of brain structural abnormalities in children with autism spectrum disorder based on artificial intelligence automatic brain segmentation technology and machine learning methods

Rationale and objectivesTo explore the characteristics of brain structure in Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to diagnose children with ASD using machine learning (ML) methods in combination with structural magnetic resonance imaging (sMRI) features. MethodsA total of 60 ASD children and 48 age- and sex-matched typically developing (TD) children were prospectively enrolled from January 2023 to April 2024. All subjects were scanned using 3D-T1 sequences. Automated brain segmentation techniques were utilized to obtain the standardized volume of each brain structure (the ratio of the absolute volume of brain structure to the whole brain volume). The standardized volumes of each brain structure in the two groups were statistically compared, and the volume data of brain areas with significant differences were combined with ML methods to diagnose and predict ASD patients. ResultsCompared with the TD group, the volumes of the right lateral orbitofrontal cortex, right medial orbitofrontal cortex, right pars opercularis, right pars triangularis, left hippocampus, bilateral parahippocampal gyrus, left fusiform gyrus, right superior temporal gyrus, bilateral insula, bilateral inferior parietal cortex, right precuneus cortex, bilateral putamen, left pallidum, and right thalamus were significantly increased in the ASD group (P< 0.05). Among six ML algorithms, support vector machine (SVM) and adaboost (AB) had better performance in differentiating subjects with ASD from those TD children, with their average area under curve (AUC) reaching 0.91 and 0.92, respectively. ConclusionAutomatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in children with autism spectrum disorder and typically developing children. Children with ASD show abnormalities in multiple brain structures, and when paired with sMRI features, ML algorithms perform well in the diagnosis of ASD.

Presubicular VIP expressing interneurons receive facilitating excitation from anterior thalamus

The presubiculum is part of the parahippocampal cortex and plays a fundamental role for orientation in space. Many principal neurons of the presubiculum signal head direction, and show persistent firing when the head of an animal is oriented in a specific preferred direction. GABAergic neurons of the presubiculum control the timing, sensitivity and selectivity of head directional signals from the anterior thalamic nuclei. However, the role of vasoactive intestinal peptide (VIP) expressing interneurons in the presubicular microcircuit has not yet been addressed. Here, we examined the intrinsic properties of VIP interneurons as well as their input connectivity following photostimulation of anterior thalamic axons. We show that presubicular VIP interneurons are more densely distributed in superficial than in deep layers. They are highly excitable. Three groups emerged from the unsupervised cluster analysis of their electrophysiological properties. We demonstrate a frequency dependent recruitment of VIP cells by thalamic afferences and facilitating synaptic input dynamics. Our data provide initial insight into the contribution of VIP interneurons for the integration of thalamic head direction information in the presubiculum.

Symptom Persistence Relates to Volume and Asymmetry of the Limbic System after Mild Traumatic Brain Injury.

Background: Persistent symptoms have been reported in up to 50% of the 27 million people with mild traumatic brain injuries (mTBI) every year. MRI findings are currently limited by low diagnostic and prognostic sensitivities, constraining the value of imaging in the stratification of patients following mTBI. Limbic system structures are promising brain regions in offering prognostic factors for symptom persistence following mTBI. The objective of this study was to associate volume and symmetry of limbic system structures with the presence and persistence of common symptoms in patients with mTBI. Methods: This study focused on 524 adults (aged 18-82), 58% female, with 82% injured in motor vehicle accidents and 28% reporting loss of consciousness (LOC). Magnetic resonance imaging (MRI) data included a sagittal 3D T1-weighted sequence with 1.2 mm slice thickness, with voxel sizes of 0.93 mm × 0.93 mm × 1.2 mm, obtained a median of 156 days after injury. Symptom diagnosis and persistence were collected retrospectively from patient medical records. Intracranial volume-adjusted regional volumes per side utilizing automated volumetric analysis (NeuroQuant®) were used to calculate total volume, laterality index, and side-independent asymmetry. Covariates included age, sex, LOC, and days from injury. Limbic volumetrics did not relate to symptom presentation, except the (-) association between headache presence and thalamus volume (adjusted odds ratio = 0.51, 95% confidence interval = 0.32, 0.85). Headache, balance problems, anxiety, and depression persistence was (-) associated with thalamus volume (hazard ratio (HR) 1.25 to 1.94). Longer persistence of balance problems was associated with (-) lateral orbitofrontal cortex volume (HR = 1.33) and (+) asymmetry of the hippocampus (HR = 0.27). Persistence of cognitive deficits was associated with (+) asymmetry in the caudal anterior cingulate (HR = 0.67). Depression persistence was associated with (+) asymmetry in the isthmus of the cingulate gyrus (HR = 5.39). Persistence of anxiety was associated with (-) volume of the parahippocampal gyrus (HR = 1.67), orbitofrontal cortex (HR > 1.97), and right-biased laterality of the entorhinal cortex (HR = 0.52). Conclusions: Relative volume and asymmetry of the limbic system structures in patients with mTBI are associated with the persistence of symptoms, particularly anxiety. The conclusions of this study are limited by the absence of a reference group with no mTBI.

Pathologic Substrates of Structural Brain Network Resilience and Topology in Parkinson Disease Decedents.

In Parkinson disease (PD), α-synuclein spreading through connected brain regions leads to neuronal loss and brain network disruptions. With diffusion-weighted imaging (DWI), it is possible to capture conventional measures of brain network organization and more advanced measures of brain network resilience. We aimed to investigate which neuropathologic processes contribute to regional network topologic changes and brain network resilience in PD. Using a combined postmortem MRI and histopathology approach, PD and control brain donors with available postmortem in situ 3D T1-weighted MRI, DWI, and brain tissue were selected from the Netherlands Brain Bank and Normal Aging Brain Collection Amsterdam. Probabilistic tractography was performed, and conventional network topologic measures of regional eigenvector centrality and clustering coefficient, and brain network resilience (change in global efficiency upon regional node failure) were calculated. PSer129 α-synuclein, phosphorylated-tau, β-amyloid, neurofilament light-chain immunoreactivity, and synaptophysin density were quantified in 8 cortical regions. Group differences and correlations were assessed with rank-based nonparametric tests, with age, sex, and postmortem delay as covariates. Nineteen clinically defined and pathology-confirmed PD (7 F/12 M, 81 ± 7 years) and 15 control (8 F/7 M, 73 ± 9 years) donors were included. With regional conventional measures, we found lower eigenvector centrality only in the parahippocampal gyrus in PD (d = -1.08, 95% CI 0.003-0.010, p = 0.021), which did not associate with underlying pathology. No differences were found in regional clustering coefficient. With the more advanced measure of brain network resilience, we found that the PD brain network was less resilient to node failure of the dorsal anterior insula compared with the control brain network (d = -1.00, 95% CI 0.0012-0.0015, p = 0.018). This change was not directly driven by neuropathologic processes within the dorsal anterior insula or in connected regions but was associated with higher Braak α-synuclein staging (rs = -0.40, p = 0.036). Although our cohort might suffer from selection bias, our results highlight that regional network disturbances are more complex to interpret than previously believed. Regional neuropathologic processes did not drive regional topologic changes, but a global increase in α-synuclein pathology had a widespread effect on brain network reorganization in PD.

Effect of Repetitive Transcranial Magnetic Stimulation on Post-Stroke Comorbid Cognitive Impairment and Depression: A Randomized Controlled Trial.

There are currently no uniform treatments for post-stroke comorbid cognitive impairment and depression (PSCCID). To verify whether repetitive transcranial magnetic stimulation (rTMS) can improve PSCCID symptoms and explore the underlying roles of resting-state functional magnetic resonance imaging (rs-fMRI). Thirty PSCCID patients were randomized in a 1 : 1 ratio to receive 4 weeks of rTMS (intervention group) or sham rTMS (control group) over the left dorsolateral prefrontal cortex (DLPFC). rs-fMRI was acquired to analyze the functional plasticity of brain regions at baseline and immediately after the last intervention. Cognition, depression status, and neural electrophysiology were improved in both intervention and control groups after treatment (p = 0.015-0.042), and the intervention group had more significant improvement than the control group. Analysis of functional connectivities (FCs) within the default mood network (DMN) showed that the connection strength of the left temporal pole/left parahippocampal cortex and right lateral temporal cortex/right retrosplenial cortex in the intervention group were enhanced compared with its pre-intervention and that in the control group after treatment (p < 0.05), and the both FC values were positively correlated with MMSE scores (p < 0.001). The intervention group had stronger FCs within the DMN compared with the control group after treatment, and some of the enhanced FCs were correlated with the P300 latency and amplitude. rTMS over the left DLPFC is an effective treatment for improving both cognitive impairment and depression among patients with PSCCID. The enhanced FCs within the DMN may serve as a compensatory functional recombination to promote clinical recovery.