Methamphetamine-related working memory difficulties underpinned by reduced frontoparietal responses.

Working memory difficulties are common, debilitating, and may pose barriers to recovery for people who use methamphetamine. Yet, little is known regarding the neural dysfunctions accompanying these difficulties. Here, we acquired cross-sectional, functional magnetic resonance imaging while people with problematic methamphetamine-use experience (MA+, n = 65) and people without methamphetamine-use experience (MA-, n = 44) performed a parametric n-back task (0-back through 2-back). Performance on tasks administered outside of the scanner, together with n-back performance, afforded to determine a latent dimension of participants' working memory ability. Behavioural results indicated that MA+ participants exhibited lower scores on this dimension compared to MA- participants (d = -1.39, p < .001). Whole-brain imaging results also revealed that MA+ participants exhibited alterations in load-induced responses predominantly in frontoparietal and default-mode areas. Specifically, while the MA- group exhibited monotonic activation increases within frontoparietal areas and monotonic decreases within default-mode areas from 0-back to 2-back, MA+ participants showed a relative attenuation of these load-induced activation patterns (d = -1.55, p < .001). Moreover, increased activations in frontoparietal areas from 0- to 2-back were related to greater working memory ability among MA+ participants (r = .560, p = .004). No such effects were observed for default-mode areas. In sum, reductions in working memory ability were observed alongside load-induced dysfunctions in frontoparietal and default-mode areas for people with problematic methamphetamine-use experience. Among them, load-induced activations within frontoparietal areas were found to have a strong and specific relationship to individual differences in working memory ability, indicating a putative neural signature of the working memory difficulties associated with chronic methamphetamine use.

Restricted Cortical Activity Involving Parietal Lobe and Sublobar Region Leads to Generalized Spike-Wave Discharges of Juvenile Myoclonic Epilepsy: Evidence from an EEG Source Localization Study.

BACKGROUND: Previous studies have localized the origin of "generalized" spike-wave discharges of idiopathic generalized epilepsies to specific brain regions. Although there are studies in juvenile myoclonic epilepsy (JME) which have investigated the origin of spike-wave discharges, reports on the propagation of discharges are sparse. OBJECTIVE: The current study investigated the propagation of spike-wave discharges in JME, which was investigated by statistically comparing the electroencephalography (EEG)-derived cortical source activity during (a) various phases of spike-wave discharge versus background (eyes closed) activity, and (b) various phases of the first spike wave versus the corresponding phase of subsequent spike waves. MATERIAL AND METHODS: Fourteen patients with JME who had generalized spike/polyspike and slow wave discharges in interictal EEG were included in the study. A total of 179 spike waves (first discernible spike wave - 55; subsequent spike waves - 124) were selected for source localization. Source analysis was carried out using exact low-resolution electromagnetic tomography (eLORETA). Statistical analyses to estimate the probability distribution of differences in cortical activity between (a) eight phases of epileptic discharge versus background (eyes closed) activity and (b) phases of the first spike wave versus the corresponding phases of subsequent spike waves were performed by paired t-tests and corrected for multiple testing using LORETA-KEY software. RESULTS: Widespread activation of cortical voxels (more than 94%) was observed during all phases of epileptic discharge except the initial phase (pre-first spike) and terminal phase (post-peak of the subsequent wave). The parietal lobe, which was the most activated lobe during the pre-first spike, was found to be the least activated during the post-peak of first and subsequent waves. More than 93% of voxels in the sublobar region were consistently activated during all eight phases of discharge. CONCLUSION: The study findings suggest that the activity generated from the restricted brain network involving parietal lobe could be propagated through sublobar structures to cause widespread cortical activation during the subsequent phases of the spike-wave cycle.

Targeting auditory verbal hallucinations in schizophrenia: effective connectivity changes induced by low-frequency rTMS.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Greater Frontoparietal Connectivity During Task Engagement Among Toddlers With Parent-Reported Inattention.

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with lifelong impairments. ADHD-related behaviors have been observed as early as toddlerhood for children who later develop ADHD. Children with ADHD have disrupted connectivity in neural circuitry involved in executive control of attention, including the prefrontal cortex (PFC) and dorsal attention network (DAN). It is not known if these alterations in connectivity can be identified before the onset of ADHD. Children (N = 51) 1.5-3 years old were assessed using functional near-infrared spectroscopy while engaging with a book. The relation between mother-reported ADHD-related behaviors and neural connectivity, computed using robust innovation-based correlation, was examined. Task engagement was high across the sample and unrelated to ADHD-related behaviors. Observed attention was associated with greater connectivity between the right lateral PFC and the right temporal parietal junction (TPJ). Children with greater ADHD-related behaviors had greater frontoparietal connectivity, particularly between the PFC bilaterally and the right TPJ. Toddlers at risk for developing ADHD may require increased frontoparietal connectivity to sustain attention. Future work is needed to examine early interventions that enhance developing attention and their effect on neural connectivity between the PFC and attention networks.

Physical activity and frontoparietal network connectivity in traumatic brain injury.

BACKGROUND: Prolonged changes to functional network connectivity as a result of a traumatic brain injury (TBI) may relate to long-term cognitive complaints reported by TBI survivors. No interventions have proven to be effective at treating long-term cognitive complaints after TBI but physical activity has been shown to promote cognitive function and modulate functional network connectivity in non-injured adults. Therefore, the objective of this study was to test if physical activity engagement was associated with functional connectivity of the cognitively relevant frontoparietal control network (FPCN) in adults with a TBI history. METHODS: In a case-control study design, resting state function magnetic resonance imaging and physical activity data from a subset of participants (18-81 years old) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study was analyzed. Fifty-seven participants reported a prior head injury with loss of consciousness and 57 age and sex matched controls were selected. Seed-based functional connectivity analyses were performed using seeds in the dorsolateral prefrontal cortex and the inferior parietal lobule, to test for differences in functional connectivity between groups, associations between physical activity and functional connectivity within TBI as well as differential associations between physical activity and functional connectivity between TBI and controls. RESULTS: Seed-based connectivity analyses from the dorsolateral prefrontal cortex showed that those with a history of TBI had decreased positive connectivity between dorsolateral prefrontal cortex and intracalcarine cortex, lingual gyrus, and cerebellum, and increased positive connectivity between dorsolateral prefrontal cortex and cingulate gyrus and frontal pole in the TBI group. Results showed that higher physical activity was positively associated with increased connectivity between the dorsolateral prefrontal cortex and inferior temporal gyrus. Differential associations were observed between groups whereby the strength of the physical activity-functional connectivity association was different between the inferior parietal lobule and inferior temporal gyrus in TBI compared to controls. DISCUSSION: Individuals with a history of TBI show functional connectivity alterations of the FPCN. Moreover, engagement in physical activity is associated with functional network connectivity of the FPCN in those with a TBI. These findings are consistent with the evidence that physical activity affects FPCN connectivity in non-injured adults; however, this effect presents differently in those with a history of TBI.

Interactive effect of air pollution and genetic risk of depression on processing speed by resting-state functional connectivity of occipitoparietal network.

BACKGROUND: Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. METHODS: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. RESULTS: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. CONCLUSIONS: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.

Symptomatology after damage to the angular gyrus through the lenses of modern lesion-symptom mapping.

Brain-behavior relationships are complex. For instance, one might know a brain region's function(s) but still be unable to accurately predict deficit type or severity after damage to that region. Here, I discuss the case of damage to the angular gyrus (AG) that can cause left-right confusion, finger agnosia, attention deficit, and lexical agraphia, as well as impairment in sentence processing, episodic memory, number processing, and gesture imitation. Some of these symptoms are grouped under AG syndrome or Gerstmann's syndrome, though its exact underlying neuronal systems remain elusive. This review applies recent frameworks of brain-behavior modes and principles from modern lesion-symptom mapping to explain symptomatology after AG damage. It highlights four major issues for future studies: (1) functionally heterogeneous symptoms after AG damage need to be considered in terms of the degree of damage to (i) different subdivisions of the AG, (ii) different AG connectivity profiles that disconnect AG from distant regions, and (iii) lesion extent into neighboring regions damaged by the same infarct. (2) To explain why similar symptoms can also be observed after damage to other regions, AG damage needs to be studied in terms of the networks of regions that AG functions with, and other independent networks that might subsume the same functions. (3) To explain inter-patient variability on AG symptomatology, the degree of recovery-related brain reorganisation needs to account for time post-stroke, demographics, therapy input, and pre-stroke differences in functional anatomy. (4) A better integration of the results from lesion and functional neuroimaging investigations of AG function is required, with only the latter so far considering AG function in terms of a hub within the default mode network. Overall, this review discusses why it is so difficult to fully characterize the AG syndrome from lesion data, and how this might be addressed with modern lesion-symptom mapping.

Articulatory-based Phonemic Paraphasia in Conduction Aphasia: A Dysfunction in Phoneme-to-Articulation Conversion Uncovered Through Crossed Aphasia.

Phonemic paraphasia, a common characteristic of conduction aphasia, has traditionally been attributed to phonological representation dysfunction. An alternative hypothesis posits that phonemic paraphasia arises from difficulty converting phonemes into their corresponding articulatory maneuvers. However, detailed case studies supporting this theory have been lacking. In this report, we present the case of a 61-year-old right-handed man with right temporo-parietal infarction who exhibited crossed aphasia characterized by typical conduction aphasia symptoms (eg, relatively fluent speech with intact comprehension, frequent phonemic paraphasia, and pronounced difficulties in oral repetition) in the absence of distorted articulation, syllable segmentation, and prosody impairment. Despite the frequent occurrence of phonemic paraphasia and articulatory challenges, our patient's phonological representations remained relatively intact. His phonemic paraphasia was often self-corrected to produce correct responses, a feature known as conduit d'approche. During the oral repetition of individual mora (ie, the smallest unit of speech in Japanese), we observed that the patient consistently traced the corresponding Hiragana phonetic symbol accurately, despite his difficulties in articulation. We substantiated this phenomenon through objective assessment and posit that it resulted from an unusual separation of language functions in crossed aphasia-specifically, a disconnection between phonological representations in the right temporo-parietal cortex and speech articulation engrams in the left hemisphere. In this case of conduction aphasia, articulatory-based phonemic paraphasia may be viewed as an inability to convert phonemes into the appropriate articulatory maneuvers rather than as phonological representation dysfunction or apraxia of speech.

Repetitive transcranial magnetic stimulation reshaped the dynamic reconfiguration of the executive and reward networks in individuals with tobacco use disorder.

BACKGROUND: Studies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear. METHODS: Using dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group. RESULTS: Compared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN. LIMITATIONS: This study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking. CONCLUSION: rTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

Transcranial direct current stimulation over the right parietal cortex improves the depressive disorder: A preliminary study.

OBJECTIVE: The right posterior parietal cortex is the core brain region of emotional processing and executive control network in the human brain, and the function of the right posterior parietal cortex is decreased in patients with major depressive disorder. This study aims to preliminarily investigate whether the excitation of the right posterior parietal cortex by transcranial direct current stimulation (tDCS) could improve their clinical symptoms. METHODS: In this study, 12 patients with major depressive disorder were given tDCS treatment at Xuanwu Hospital of Capital Medical University and the First Hospital of Hebei Medical University. The stimulating electrode (anode) was placed on the patients' right parietal cortex, whereas the reference electrode (cathode) was placed on the patients' left mastoid. The stimulation intensity was set as 2.0 mA. The patients with depressive disorder were treated for 20 min at a time twice a day for 14 consecutive days. The severity of the clinical symptoms was evaluated using the Hamilton Depression Rating Scale-17 (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS) at before and right after treatment. RESULTS: The HDRS-17 scores of patients with depressive disorder decreased significantly following the tDCS treatment compared with those before treatment (p < .001). Further analysis revealed that the patients' anxiety/somatization, cognitive deficit, retardation, and sleep disorder scores all decreased significantly after the tDCS treatment (p < .05), although there was no significant change in their weight. Moreover, the patients' HARS scores decreased significantly after the tDCS treatment when compared with those before treatment (p < .01). CONCLUSION: The right parietal cortex may be another key stimulation targets to improving the efficacy of tDCS treatment to the patients with major depressive disorder.

More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Toward a neurocircuit-based sequential transcranial magnetic stimulation treatment of pediatric bipolar II disorder.

BACKGROUND: Abnormalities in large-scale neuronal networks-the frontoparietal central executive network (CEN)-are consistent findings in bipolar disorder and potential therapeutic targets for transcranial magnetic stimulation (TMS). OBJECTIVE: The present study aimed to assess the effects of CEN neurocircuit-based sequential TMS on the clinical symptoms and cognitive functions of adolescents with bipolar II disorder. METHODS: The study was a single-blinded, randomized, placebo-control trial. Participants with DSM-5-defined bipolar disorder II were recruited and randomized to receive either a sham treatment (n = 20) or an active TMS treatment (n = 22). The active group patients were taking medication, with intermittent theta burst stimulation (iTBS) treatment provided as adjunctive treatment targeting the left DLPFC, the left ITG, and the left PPC nodes consecutively. Patients completed the measurements of HAMD and the Das-Naglieri Cognition Assessment System at baseline and 3 weeks after the intervention. RESULTS: A significant group-by-time interaction was observed in the HAMD, total cognition, and planning. Post-hoc analysis revealed that patients in the active group significantly improved HAMD scores following neurostimulation. Moreover, within-subject analysis indicated that the active group significantly improved in scores of total cognition and planning, while the sham group did not. No significant differences were seen in the other cognitive measures. CONCLUSION: The neurocircuit-based sequential TMS protocol targeting three CEN nodes, in conjunction with medication, safely and effectively improved depressive symptoms and cognitive function in adolescents with bipolar II disorder.

Sex moderates the effect of anhedonia on parietal alpha asymmetry.

Anhedonia, a transdiagnostic symptom present in many neuropsychiatric disorders, differs in males and females. Parietal EEG alpha asymmetry is associated with reduced arousal and low positive emotionality, and is, therefore, a promising neurophysiologic biomarker of anhedonia. To date, however, no prior studies have determined whether this measure captures sex differences in anhedonic expression. This preliminary study (N = 36) investigated whether anhedonia severity is associated with EEG resting-state parietal alpha asymmetry in adults and whether sex moderates this relationship. Results showed that there was a significant moderating effect of sex such that, only for females, higher levels of anhedonia were associated with increased parietal alpha asymmetry. These findings suggest that parietal alpha asymmetry is a promising biomarker of anhedonia severity in female adults and reinforces the need to account for sex differences in future research.

Exploring the neurocognitive correlates of suicidal ideation in major depressive disorder: The role of frontoparietal and default mode networks.

Suicidal ideation (SI) is a common symptom of major depressive disorder (MDD), often accompanied by cognitive alterations and emotional dysregulation. However, it is unclear whether cognitive dysfunction in patients with MDD is related to the presence or absence of SI and impaired connectivity within or between large-scale neurocognitive networks. Previous studies have shown that the frontoparietal network (FPN) and default mode network (DMN) are critical for cognitive control and emotional regulation. Participants were 51 MDD patients with suicidal ideation (MDDSI), 52 MDD patients without suicidal ideation (MDDNSI), and 55 healthy controls (HC). Using areas located within FPN and DMN networks as regions of interest (ROIs), we compared the cognitive performance of the three groups and the strength of the resting state functional connections (RSFC) within and between the FPN and DMN networks. Additionally, we examined the correlation between the strength of FC within the FPN and cognitive function in the SI group. Furthermore, network-based statistics (NBS) were used to correct for the strength of FPN and DMN functional connections. The study identified significant cognitive deficits in MDD patients. Reduced strength of FC was observed within the FPN and DMN networks in the SI group compared to the NSI group. In the SI group, the strength of FC within the FPN network was positively correlated with attention/vigilance. These insights underscore the critical roles of the FPN and DMN in the suicidal ideation, shedding light on the cognitively relevant neurobiological characteristics of MDDSI, providing new insights into the neural mechanisms of MDDSI. URL: https://www.chictr.org.cn/bin/project/edit?pid=131537. Registration number: ChiCTR2100049646.

The developmental phenotype of motor delay in extremely preterm infants following early-life respiratory adversity is influenced by brain dysmaturation in the parietal lobe.

BACKGROUND: Research indicates that preterm infants requiring prolonged mechanical ventilation often exhibit suboptimal neurodevelopment at follow-up, coupled with altered brain development as detected by magnetic resonance imaging (MRI) at term-equivalent age (TEA). However, specific regions of brain dysmaturation and the subsequent neurodevelopmental phenotype following early-life adverse respiratory exposures remain unclear. Additionally, it is uncertain whether brain dysmaturation mediates neurodevelopmental outcomes after respiratory adversity. This study aims to investigate the relationship between early-life adverse respiratory exposures, brain dysmaturation at TEA, and the developmental phenotype observed during follow-up in extremely preterm infants. METHODS: 89 infants born < 29 weeks' gestation from 2019 to 2021 received MRI examinations at TEA for structural and lobe brain volumes, which were adjusted with sex-and-postmenstrual-age expected volumes for volume residuals. Assisted ventilation patterns in the first 8 postnatal weeks were analyzed using kmlShape analyses. Patterns for motor, cognition, and language development were evaluated from corrected age 6 to 12 months using Bayley Scales of Infant Development, third edition. Mediation effects of brain volumes between early-life respiratory exposures and neurodevelopmental phenotypes were adjusted for sex, gestational age, maternal education, and severe brain injury. RESULTS: Two distinct respiratory trajectories with varying severity were identified: improving (n = 35, 39%) and delayed improvement (n = 54, 61%). Compared with the improving group, the delayed improvement group exhibited selectively reduced brain volume residuals in the parietal lobe (mean - 4.9 cm3, 95% confidence interval - 9.4 to - 0.3) at TEA and lower motor composite scores (- 8.7, - 14.2 to - 3.1) at corrected age 12 months. The association between delayed respiratory improvement and inferior motor performance (total effect - 8.7, - 14.8 to - 3.3) was partially mediated through reduced parietal lobe volume (natural indirect effect - 1.8, - 4.9 to - 0.01), suggesting a mediating effect of 20%. CONCLUSIONS: Early-life adverse respiratory exposure is specifically linked to the parietal lobe dysmaturation and neurodevelopmental phenotype of motor delay at follow-up. Dysmaturation of the parietal lobe serves as a mediator in the connection between respiratory adversity and compromised motor development. Optimizing respiratory critical care may emerge as a potential avenue to mitigate the consequences of altered brain growth and motor developmental delay in this extremely preterm population.

Frontoparietal-Striatal Network and Nucleus Basalis Modulation in Patients With Parkinson Disease and Gait Disturbance.

BACKGROUND AND OBJECTIVES: Neural computations underlying gait disorders in Parkinson disease (PD) are multifactorial and involve impaired expression of stereotactic locomotor patterns and compensatory recruitment of cognitive functions. This study aimed to clarify the network mechanisms of cognitive contribution to gait control and its breakdown in patients with PD. METHODS: Patients with PD were instructed to walk at a comfortable pace on a mat with pressure sensors. The characterization of cognitive-motor interplay was enhanced by using a gait with a secondary cognitive task (dual-task condition) and a gait without additional tasks (single-task condition). Participants were scanned using 3-T MRI and 123I-ioflupane SPECT. RESULTS: According to gait characteristics, cluster analysis assisted by a nonlinear dimensionality reduction technique, t-distributed stochastic neighbor embedding, categorized 56 patients with PD into 3 subpopulations. The preserved gait (PG) subgroup (n = 23) showed preserved speed and variability during gait, both with and without additional cognitive load. Compared with the PG subgroup, the mildly impaired gait (MIG) subgroup (n = 16) demonstrated deteriorated gait variability with additional cognitive load and impaired speed and gait variability without additional cognitive load. The severely impaired gait (SIG) subgroup (n = 17) revealed the slowest speed and highest gait variability. In addition, group differences were found in attention/working memory and executive function domains, with the lowest performance in the SIG subgroup than in the PG and MIG subgroups. Using resting-state functional MRI, the SIG subgroup demonstrated lower functional connectivity of the left and right frontoparietal network (FPN) with the caudate than the PG subgroup did (left FPN, d = 1.21, p < 0.001; right FPN, d = 1.05, p = 0.004). Cortical thickness in the FPN and 123I-ioflupane uptake in the striatum did not differ among the 3 subgroups. By contrast, the severity of Ch4 density loss was significantly correlated with the level of functional connectivity degradation of the FPN and caudate (left FPN-caudate, r = 0.27, p = 0.04). DISCUSSION: These findings suggest that the functional connectivity of the FPN with the caudate, as mediated by the cholinergic Ch4 projection system, underlies the compensatory recruitment of attention and executive function for damaged automaticity in gait in patients with PD.

Cerebellum and social abilities: A structural and functional connectivity study in a transdiagnostic sample.

The cerebellum has been involved in social abilities and autism. Given that the cerebellum is connected to the cortex via the cerebello-thalamo-cortical loop, the connectivity between the cerebellum and cortical regions involved in social interactions, that is, the right temporo-parietal junction (rTPJ) has been studied in individuals with autism, who suffer from prototypical deficits in social abilities. However, existing studies with small samples of categorical, case-control comparisons have yielded inconsistent results due to the inherent heterogeneity of autism, suggesting that investigating how clinical dimensions are related to cerebellar-rTPJ functional connectivity might be more relevant. Therefore, our objective was to study the functional connectivity between the cerebellum and rTPJ, focusing on its association with social abilities from a dimensional perspective in a transdiagnostic sample. We analyzed structural magnetic resonance imaging (MRI) and functional MRI (fMRI) scans obtained during naturalistic films watching from a large transdiagnostic dataset, the Healthy Brain Network (HBN), and examined the association between cerebellum-rTPJ functional connectivity and social abilities measured with the social responsiveness scale (SRS). We conducted univariate seed-to-voxel analysis, multivariate canonical correlation analysis (CCA), and predictive support vector regression (SVR). We included 1404 subjects in the structural analysis (age: 10.516 ± 3.034, range: 5.822-21.820, 506 females) and 414 subjects in the functional analysis (age: 11.260 ± 3.318 years, range: 6.020-21.820, 161 females). Our CCA model revealed a significant association between cerebellum-rTPJ functional connectivity, full-scale IQ (FSIQ) and SRS scores. However, this effect was primarily driven by FSIQ as suggested by SVR and univariate seed-to-voxel analysis. We also demonstrated the specificity of the rTPJ and the influence of structural anatomy in this association. Our results suggest that there is a complex relationship between cerebellum-rTPJ connectivity, social performance and IQ. This relationship is specific to the cerebellum-rTPJ connectivity, and is largely related to structural anatomy in these two regions. PRACTITIONER POINTS: We analyzed cerebellum-right temporoparietal junction (rTPJ) connectivity in a pediatric transdiagnostic sample. We found a complex relationship between cerebellum and rTPJ connectivity, social performance and IQ. Cerebellum and rTPJ functional connectivity is related to structural anatomy in these two regions.

Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in a cohort of patients with traumatic disorders of consciousness.

Neuroimaging studies have suggested an important role for the default mode network (DMN) in disorders of consciousness (DoC). However, the extent to which DMN connectivity can discriminate DoC states-unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS)-is less evident. Particularly, it is unclear whether effective DMN connectivity, as measured indirectly with dynamic causal modelling (DCM) of resting EEG can disentangle UWS from healthy controls and from patients considered conscious (MCS+). Crucially, this extends to UWS patients with potentially "covert" awareness (minimally conscious star, MCS*) indexed by voluntary brain activity in conjunction with partially preserved frontoparietal metabolism as measured with positron emission tomography (PET+ diagnosis; in contrast to PET- diagnosis with complete frontoparietal hypometabolism). Here, we address this gap by using DCM of EEG data acquired from patients with traumatic brain injury in 11 UWS (6 PET- and 5 PET+) and in 12 MCS+ (11 PET+ and 1 PET-), alongside with 11 healthy controls. We provide evidence for a key difference in left frontoparietal connectivity when contrasting UWS PET- with MCS+ patients and healthy controls. Next, in a leave-one-subject-out cross-validation, we tested the classification performance of the DCM models demonstrating that connectivity between medial prefrontal and left parietal sources reliably discriminates UWS PET- from MCS+ patients and controls. Finally, we illustrate that these models generalize to an unseen dataset: models trained to discriminate UWS PET- from MCS+ and controls, classify MCS* patients as conscious subjects with high posterior probability (pp > .92). These results identify specific alterations in the DMN after severe brain injury and highlight the clinical utility of EEG-based effective connectivity for identifying patients with potential covert awareness.

Additive effects of depression and obesity on neural correlates of inhibitory control.

BACKGROUND: Depression and obesity are associated with impaired inhibitory control. Behavioral evidence indicates an exacerbating additive effect when both conditions co-occur. However, the underlying neural mechanisms remain unclear. Moreover, systemic inflammation affects neurocognitive performance in both individuals with depression and obesity. Here, we investigate additive effects of depression and obesity on neural correlates of inhibitory control, and examine inflammation as a connecting pathway. METHODS: We assessed inhibitory control processing in 64 individuals with obesity and varying degrees of depressed mood by probing neural activation and connectivity during an fMRI Stroop task. Additionally, we explored associations of altered neural responses with individual differences in systemic inflammation. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. RESULTS: Concurrent depression and obesity were linked to increased functional connectivity between the supplementary motor area and precuneus and between the inferior occipital and inferior parietal gyrus. Exploratory analysis revealed that circulating inflammation markers, including plasma leptin, IL-6, IL-8, and CCL-3 correlated with the additive effect of depression and obesity on altered functional connectivity. LIMITATIONS: The observational design limits causal inferences. Future research employing longitudinal or intervention designs is required to validate these findings and elucidate causal pathways. CONCLUSION: These findings suggest increased neural crosstalk underlying impaired inhibitory control in individuals with concurrent obesity and depressed mood. Our results support a model of an additive detrimental effect of concurrent depression and obesity on neurocognitive functioning, with a possible role of inflammation.

Comparisons of the amplitude of low-frequency fluctuation and functional connectivity in major depressive disorder and social anxiety disorder: A resting-state fMRI study.

BACKGROUND: Studies comparing the brain functions of major depressive disorder (MDD) and social anxiety disorder (SAD) at the regional and network levels remain scarce. This study aimed to elucidate their pathogenesis using neuroimaging techniques and explore biomarkers that can differentiate these disorders. METHODS: Resting-state fMRI data were collected from 48 patients with MDD, 41 patients with SAD, and 82 healthy controls. Differences in the amplitude of low-frequency fluctuations (ALFF) among the three groups were examined to identify regions showing abnormal regional spontaneous activity. A seed-based functional connectivity (FC) analysis was conducted using ALFF results as seeds and different connections were identified between regions showing abnormal local spontaneous activity and other regions. The correlation between abnormal brain function and clinical symptoms was analyzed. RESULTS: Patients with MDD and SAD exhibited similar abnormal ALFF and FC in several brain regions; notably, FC between the right superior frontal gyrus (SFG) and the right posterior supramarginal gyrus (pSMG) in patients with SAD was negatively correlated with depressive symptoms. Furthermore, patients with MDD showed higher ALFF in the right SFG than HCs and those with SAD. LIMITATION: Potential effects of medications, comorbidities, and data type could not be ignored. CONCLUSION: MDD and SAD showed common and distinct aberrant brain function patterns at the regional and network levels. At the regional level, we found that the ALFF in the right SFG was different between patients with MDD and those with SAD. At the network level, we did not find any differences between these disorders.