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The study was designed to analyze the nNOS positive neurons present in the indusium griseum by describing their distribution and morphology. To this purpose, sagittal serial sections from paraffin or frozen autopsy specimens of corpus callosum including the overlying indusium griseum were processed by immunohistochemistry and immunofluorescence, using an antibody against the neuronal form of the enzyme nitric oxyde synthase. To test the specificity of the antibody used, Western Blot was performed in the indusium griseum of the same specimens. The stainings revealed the presence of many neuronal nitric oxyde synthase-immunopositive neurons in human indusium griseum, located along both rostral-caudal and medio-lateral directions. In particular, they were more numerous 1 mm apart from the midline, and their number peaked over the body of the corpus callosum. They showed different morphologies; in some cases, they were located at the boundary between indusium griseum and corpus callosum, more densely packed in proximity to the pial arteries penetrating into the corpus callosum. The significant presence and distribution of neuronal nitric oxyde synthase-immunopositive neurons suggests that indusium griseum likely plays a functional role in the neurovascular regulation within the corpus callosum. Graphical abstract Schematic representation of human adult IG and the neurovascular unit originating from sopracallosal artery (Sca) that branches into smaller arterioles (Br) (created in PowerPoint). The arterioles cross the three layers of IG (layers I, II and III) and penetrate into the CC separated from IG by the Virchow-Robin space (VRs). As the arterioles go deeper, this space disappears and the vascular basement membrane comes into direct contact with the astrocytic end-feets (intracallosal arterioles and capillaries). nNOS-immunopositive neurons (nNOSIP N) surround the arterioles and control the vasomotore tone secreting nitric oxyde (NO). Two morphological types of nNOSIP N can be appreciated by the use of different colors: fusiform (blue) and ovoidal (pink). Also NeuN-immunopositive neurons (N) and many astrocytes (As) are present, more numerous in IG than in CC.

The human dorsolateral prefrontal cortex (DLPFC; approximately corresponding to Brodmann areas 9 and 46) has demonstrable roles in diverse executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning. However, it remains unclear whether this is the result of one functionally homogeneous region or whether there are functional subdivisions within the DLPFC. Here, we divided the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically and explored their respective patterns of structural and functional connectivity. In vivo probabilistic tractography (11 females and 13 males) and resting-state functional magnetic resonance imaging (fMRI; 57 females and 21 males) were employed to map out the patterns of connectivity from each DLPFC subregion. Structural connectivity demonstrated graded intraregional connectivity within the DLPFC. The patterns of structural connectivity between the DLPFC subregions and other cortical areas revealed that the dorsal-rostral subregions connections were restricted to other frontal and limbic areas, whereas the ventral-caudal region was widely connected to frontal, parietal, and limbic cortex. Functional connectivity analyses demonstrated that subregions of DLPFC were strongly interconnected to each other. The dorsal subregions were associated with the default mode network (DMN), while middle dorsal-rostral subregions were linked with the multiple demand network (MDN). The ventral-caudal subregion showed increased functional coupling with both DMN and MDN. Our results suggest that the connectivity of the DLPFC may be subdivided along a dorsorostral-ventrocaudal axis with differing (albeit graded) patterns of connectivity reflecting the integrative executive function of the DLPFC.SIGNIFICANCE STATEMENTResearch has shown that the dorsolateral prefrontal cortex (DLPFC) plays a role in various executive functions. By dividing the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically, we explored their patterns of structural and functional connectivity. The patterns of connectivity within DLPFC subregions demonstrated graded intraregional connectivity. There were distinctive patterns of connectivity with other cortical areas in dorsal-rostral and ventral-caudal DLPFC subregions. Divisions across DLPFC subregions seem to align with their structural and functional connectivity. Our results suggest that DLPFC may be subdivided by the diagonal axis of the dorsal-ventral axis and rostral-caudal axis, supporting the framework of a functional organization along the anterior-posterior axis in the lateral PFC.

Background Initial observations with the human electroencephalogram (EEG) have interpreted slow oscillations (SOs) of the EEG during deep sleep (N3) as reflecting widespread surface-negative traveling waves that originate in frontal regions and propagate across the neocortex. However, mapping SOs with a high-density array shows the simultaneous appearance of posterior positive voltage fields in the EEG at the time of the frontal-negative fields, with the typical inversion point (apparent source) around the temporal lobe. Methods Overnight 256-channel EEG recordings were gathered from 10 healthy young adults. Individual head conductivity models were created using each participant's own structural MRI. Source localization of SOs during N3 was then performed. Results Electrical source localization models confirmed that these large waves were created by focal discharges within the ventral limbic cortex, including medial temporal and caudal orbitofrontal cortex. Conclusions Although the functional neurophysiology of deep sleep involves interactions between limbic and neocortical networks, the large EEG deflections of deep sleep are not created by distributed traveling waves in lateral neocortex but instead by relatively focal limbic discharges.

Background Researchers have proposed that impaired sleep may be a causal link in the progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Several recent findings suggest that enhancing deep sleep (N3) may improve neurological health in persons with MCI, and buffer the risk for AD. Specifically, Transcranial Electrical Stimulation (TES) of frontal brain areas, the inferred source of the Slow Oscillations (SOs) of N3 sleep, can extend N3 sleep duration and improve declarative memory for recently learned information. Recent work in our laboratory using dense array Electroencephalography (dEEG) localized the sources of SOs to anterior limbic sites – suggesting that targeting these sites with TES may be more effective for enhancing N3. Methods For the present study, we recruited 13 healthy adults (M = 42 years) to participate in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic areas and a sham stimulation (placebo). We used a convolutional neural network, trained and tested on professionally scored EEG sleep staging, to predict sleep stages for each recording. Results When compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep. TES also significantly increased spectral power in the 0.5–1 Hz frequency band (relative to pre-TES epochs) in left temporoparietal and left occipital scalp regions compared to sham. Conclusion These results suggest that even low-level TES, when specifically targeting anterior limbic sites, can increase deep (N3) sleep and thereby contribute to healthy sleep quality.

Background White matter energy supply to oligodendrocytes and the axonal compartment is crucial for normal axonal function. Although gray matter glucose hypometabolism is extensively reported in Alzheimer's disease (AD), glucose and ketones, the brain's two main fuels, are rarely quantified in white matter in AD. Objective Using a dual-tracer PET method combined with a fascicle-specific diffusion MRI approach, robust to white matter hyper intensities and crossing fibers, we aimed to quantify both glucose and ketone metabolism in specific white matter fascicles associated with mild cognitive impairment (MCI; n = 51) and AD (n = 13) compared to cognitively healthy age-matched controls (Controls; n = 14). Methods Eight white matter fascicles of the limbic lobe and corpus callosum were extracted and analyzed into fascicle profiles of five sections. Glucose (18F-fluorodeoxyglucose) and ketone (11C-acetoacetate) uptake rates, corrected for partial volume effect, were calculated along each fascicle. Results The only fascicle with significantly lower glucose uptake in AD compared to Controls was the left posterior cingulate segment of the cingulum (-22%; p = 0.016). Non-significantly lower glucose uptake in this fascicle was also observed in MCI. In contrast to glucose, ketone uptake was either unchanged or higher in sections of the fornix and parahippocampal segment of the cingulum in AD. Conclusion To our knowledge, this is the first report of brain fuel uptake calculated along white matter fascicles in humans. Energetic deterioration in white matter in AD appears to be specific to glucose and occurs first in the posterior cingulum.

Background and aimsThe working memory (WM) ability of internet addicts and the topology underlying the WM processing in internet addiction (IA) are poorly understood. In this study, we employed a graph theoretical framework to characterize the topological properties of the IA brain network in the source cortical space during WM task.MethodsA sample of 24 subjects with IA and 23 matched healthy controls (HCs) performed visual 2-back task. Exact Low Resolution Electromagnetic Tomography was adopted to project the pre-processed EEG signals into source space. Subsequently, Lagged phase synchronization was calculated between all pairs of Brodmann areas, the graph theoretical approaches were then employed to estimate the brain topological properties of all participants during the WM task.ResultsWe found better WM behavioral performance in IA subjects compared with the HCs. Moreover, compared to the HC group, more integrated and hierarchical brain network was revealed in the IA subjects in alpha band. And altered regional centrality was mainly resided in frontal and limbic lobes. In addition, significant relationships between the IA severity and the significant altered graph indices were found.ConclusionsIn conclusion, these findings provide evidence to support the notion that altered topological configuration may underline changed WM function observed in IA.

Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9–19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more stability across most networks, unpredictability was associated with stability only in SAL connectivity, and threat was associated with stability in FPN and DMN-SAL connectivity. In youth exposed to higher levels of any adversity, lower initial levels and more stability in connectivity were related to smaller increases in internalizing symptoms. Our findings suggest that whereas deprivation is associated with widespread neurodevelopmental differences in cognitive and emotion processing networks, unpredictability is related selectively to salience detection circuitry. Studies with wider developmental windows should examine whether these neurodevelopmental alterations are adaptive or serve to maintain internalizing symptoms.

Von Economo neurons (VENs) have been mentioned in the medical literature since the second half of the 19th century; however, it was not until the second decade of the 20th century that their cytomorphology was described in detail. To date, VENs have been found in limbic sectors of the frontal, temporal and insular lobes. In humans, their density seems to decrease in the caudo-rostral and ventro-dorsal direction; that is, from the anterior regions of the cingulate and insular cortices towards the frontal pole and the superior frontal gyrus. Several studies have provided similar descriptions of the shape of the VEN soma, but the size of the soma varies from one cortical region to another. There is consensus among different authors about the selective vulnerability of VENs in certain pathologies, in which a deterioration of the capacities involved in social behaviour is observed. In this review, we propose that the restriction of VENs towards the sectors linked to limbic information processing in Homo sapiens gives them a possible functional role in relation to the structures in which they are located. However, given the divergence in characteristics such as location, density, size and biochemical profile among VENs of different cortical sectors, the activities in which they participate could allow them to partake in a wide spectrum of neurological functions, including autonomic responses and executive functions.

The neural mechanisms involved in the processing of vocalizations and music were compared, in order to observe possible similarities in the encoding of their emotional content. Positive and negative emotional vocalizations (e.g. laughing, crying) and violin musical stimuli digitally extracted from them were used as stimuli. They shared the melodic profile and main pitch/frequency characteristics. Participants listened to vocalizations or music while detecting rare auditory targets (bird tweeting, or piano's arpeggios). EEG was recorded from 128 sites. P2, N400 and Late positivity responses of ERPs were analysed. P2 peak was earlier in response to vocalizations, while P2 amplitude was larger to positive than negative stimuli. N400 was greater to negative than positive stimuli. LP was greater to vocalizations than music and to positive than negative stimuli. Source modelling using swLORETA suggested that, among N400 generators, the left middle temporal gyrus and the right uncus responded to both music and vocalizations, and more to negative than positive stimuli. The right parahippocampal region of the limbic lobe and the right cingulate cortex were active during music listening, while the left superior temporal cortex only responded to human vocalizations. Negative stimuli always activated the right middle temporal gyrus, whereas positively valenced stimuli always activated the inferior frontal cortex. The processing of emotional vocalizations and music seemed to involve common neural mechanisms. Notation obtained from acoustic signals showed how emotionally negative stimuli tended to be in Minor key, and positive stimuli in Major key, thus shedding some lights on the brain ability to understand music.

International audience; The subthalamic nucleus (STN) receives direct cortical inputs which constitute the so-called hyperdirect pathway. In monkeys, motor cortices innervate the whole extent of the STN whereas limbic cortices innervate only its anteromedial part extending more medially outside the nucleus. Tractography studies in humans have also identified motor cortical inputs to the STN, but little is known about the associative and limbic cortical projections. Therefore, the aim of this study was to investigate the anatomo-functional organization of the cortical projections to the STN and to the adjacent medial subthamic region (MSR). We used diffusion-weighted imaging-based tractography acquired from 30 subjects from the Human Connectome Project. We performed a whole-brain probabilistic tractography using MRTrix and extracted streamlines of interest between 39 cortical masks and both the STN and the MSR to provide track-density maps. Agglomerative clustering method was used to classify the voxels of the regions of interest. We found that the STN receives major inputs from the sensorimotor cortices and few inputs from the limbic cortices. On the other hand, the MSR receives mainly cortical limbic projections and few from the sensorimotor cortices. Weak connections were found between the associative cortices and both the STN and the MSR. We found a dominant motor cluster located in the posterolateral STN, a limbic cluster located medially in the MSR, and an intermediate motor-limbic cluster in between. Our findings show that the hyperdirect pathway is anatomo-functionally organized with a poor participation of associative cortices.

Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache accompanying functionally and structurally maladaptive changes in brain. As the headache days/month is often measured by patient self‐report and tends to be overestimated than actually experienced, the possibility of using neuroimaging data to predict migraine attack frequency is of great interest. To identify neuroimaging features that could objectively evaluate patients' headache days, a total of 179 migraineurs were recruited from two data center with one dataset used as the training/test cohort and the other used as the validating cohort. The guidelines for controlled trials of prophylactic treatment of chronic migraine in adults were used to identify the frequency of attacks and migraineurs were divided into low (MOl) and high (MOh) subgroups. Whole‐brain functional connectivity was used to build multivariate logistic regression models with model iteration optimization to identify MOl and MOh. The best model accurately discriminated MOh from MOl with AUC of 0.91 (95%CI [0.86, 0.95]) in the training/test cohort and 0.79 in the validating cohort. The discriminative features were mainly located within the limbic lobe, frontal lobe, and temporal lobe. Permutation tests analysis demonstrated that the classification performance of these features was significantly better than chance. Furthermore, the indicator of functional connectivity had a higher odds ratio than behavioral variables with implementing a holistic regression analysis. The current findings suggested that the migraine attack frequency could be distinguished by using machine‐learning algorithms, and highlighted the role of brain functional connectivity in revealing underlying migraine‐related neurobiology.

Objective:Bilateral anterior capsulotomy (BAC) is one of the ablative neurosurgical procedures used to treat major depressive disorder or obsessive-compulsive disorder when all other therapies fail. Tristolysis, a reduction in sadness, is the most striking clinical effect of BAC and is seen in the first 1 to 2 weeks after surgery. This retrospective study measured regional cerebral blood flow (rCBF) following surgery to identify which cortical regions were impacted and could account for this clinical effect.Methods:All patients had their capsulotomies done in Vancouver by the same team. Pre- and postoperative single-photon emission computed tomography perfusion scans were analyzed for 10 patients with major depressive disorder and 3 with obsessive-compulsive disorder. rCBF was measured semiquantitatively by calculating the ratio between an identified region of interest and a whole brain reference area.Results:Decreased rCBF was found in the paraterminal gyri. Increased rCBF was found in the dorsolateral prefrontal cortices and in the left lateral temporal lobe.Conclusions:BAC causes hypoactivity in the paraterminal gyri and is the most likely explanation for its tristolytic effect, suggesting that the paraterminal gyrus is the limbic cortical locus for the emotion of sadness. Increased activity in the dorsolateral prefrontal cortices may be occurring via connectional diaschisis, and suppression by overactive paraterminal gyri during depression may account for some of the neurocognitive deficits observed during depressive episodes.

BACKGROUND: Clinical levels of social anxiety disorder (SAD) often appear during childhood and rise to a peak during late adolescence. The temperament trait behavioral inhibition (BI), evident early in childhood, has been linked to increased risk for SAD. Functional and structural variation in brain regions associated with the identification of, and response to, fear may support the BI-SAD relation. While relevant functional studies are emerging, the few extant structural studies have focused on adult samples with mixed findings. METHODS: A moderated-mediation model was used to examine the relations between BI, SAD symptoms, and brain-volume individual differences in a sample of children at risk for anxiety (ages 9–12; N=130, 52 BI). RESULTS: Our findings indicate that at higher levels of BI, children with smaller anterior insula volumes showed stronger correlations between BI and SAD. In addition, larger ventrolateral prefrontal cortex (vlPFC) volumes were associated with fewer SAD symptoms. CONCLUSIONS: These findings support previous reports linking SAD levels with variations in volume and reactivity in both limbic (insula) and prefrontal (vlPFC) regions. These findings set the foundation for further examination of networks of neural structures that influence the transition from BI to SAD across development, helping further clarify mechanisms of risk and resilience. The data that support the findings of this study are openly available in clinical trial registration information— http://clinicaltrials.gov/; Attention and Social Behavior in Children (BRAINS); .

Mechanisms and predictors for the successful treatment of anxiety and depression have been elusive, limiting the effectiveness of existing treatments and curtailing the development of new interventions. In this study, we evaluated the utility of three widely used neural probes of emotion (experience, regulation, and perception) in their ability to predict symptom improvement and correlate with symptom change following two first-line treatments—selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Fifty-five treatment-seeking adults with anxiety and/or depression were randomized to 12 weeks of SSRI or CBT treatment (ClinicalTrials.gov identifier: NCT01903447). Functional magnetic resonance imaging (fMRI) was used to examine frontolimbic brain function during emotion experience, regulation, and perception, as probed by the Emotion Regulation Task (ERT; emotion experience and regulation) and emotional face assessment task (EFAT; emotion perception). Brain function was then related to anxiety and depression symptom change. Results showed that both SSRI and CBT treatments similarly attenuated insula and amygdala activity during emotion perception, and greater treatment-related decrease in insula and amygdala activity was correlated with greater reduction in anxiety symptoms. Both treatments also reduced amygdala activity during emotion experience but brain change did not correlate with symptom change. Lastly, greater pre-treatment insula and amygdala activity during emotion perception predicted greater anxiety and depression symptom improvement. Thus, limbic activity during emotion perception is reduced by both SSRI and CBT treatments, and predicts anxiety and depression symptom improvement. Critically, neural reactivity during emotion perception may be a non-treatment-specific mechanism for symptom improvement.

The classical theory of cortical systematic variation has been independently described in reptiles, monotremes, marsupials and placental mammals, including primates, suggesting a common bauplan in the evolution of the cortex. The Structural Model is based on the systematic variation of the cortex and is a platform for advancing testable hypotheses about cortical organization and function across species, including humans. The Structural Model captures the overall laminar structure of areas by dividing the cortical architectonic continuum into discrete categories (cortical types), which can be used to test hypotheses about cortical organization. By type, the phylogenetically ancient limbic cortices ─ which form a ring at the base of the cerebral hemisphere ─ are agranular if they lack layer IV, or dysgranular if they have an incipient granular layer IV. Beyond the dysgranular areas, eulaminate type cortices have six layers. The number and laminar elaboration of eulaminate areas differs depending on species or cortical system within a species. The construct of cortical type retains the topology of the systematic variation of the cortex and forms the basis for a predictive Structural Model, which has successfully linked cortical variation to the laminar pattern and strength of cortical connections, the continuum of plasticity and stability of areas, the regularities in the distribution of classical and novel markers, and the preferential vulnerability of limbic areas to neurodegenerative and psychiatric diseases. The origin of cortical types has been recently traced to cortical development, and helps explain the variability of diseases with an onset in ontogeny.

To uncover the ontogenesis of the human indusium griseum (IG), 28 post-mortem fetal human brains, 12–40 postconceptional weeks (PCW) of age, and 4 adult brains were analyzed immunohistochemically and compared with post-mortem magnetic resonance imaging (MRI) of 28 fetal brains (14–41 PCW). The morphogenesis of the IG occurred between 12 and 15 PCW, transforming the bilateral IG primordia into a ribbon-like cortical lamina. The histogenetic transition of sub-laminated zones into the three-layered cortical organization occurred between 15 and 35 PCW, concomitantly with rapid cell differentiation that occurred from 18 to 28 PCW and the elaboration of neuronal connectivity during the entire second half of gestation. The increasing number of total cells and neurons in the IG at 25 and 35 PCW confirmed its continued differentiation throughout this period. High-field 3.0 T post-mortem MRI enabled visualization of the IG at the mid-fetal stage using T2-weighted sequences. In conclusion, the IG had a distinct histogenetic differentiation pattern than that of the neighboring intralimbic areas of the same ontogenetic origin, and did not show any signs of regression during the fetal period or postnatally, implying a functional role of the IG in the adult brain, which is yet to be disclosed.

Brain–computer interfaces (BCIs) are capable of translating human intentions into signals controlling an external device to assist patients with severe neuromuscular disorders. Prior work has demonstrated that participants with mindfulness meditation experience evince improved BCI performance, but the underlying neural mechanisms remain unclear. Here, we conducted a large-scale longitudinal intervention study by training participants in mindfulness-based stress reduction (MBSR; a standardized mind–body awareness training intervention), and investigated whether and how short-term MBSR affected sensorimotor rhythm (SMR)-based BCI performance. We hypothesize that MBSR training improves BCI performance by reducing mind wandering and enhancing self-awareness during the intentional rest BCI control, which would mainly be reflected by modulations of default-mode network and limbic network activity. We found that MBSR training significantly improved BCI performance compared to controls and these behavioral enhancements were accompanied by increased frontolimbic alpha activity (9–15 Hz) and decreased alpha connectivity among limbic network, frontoparietal network, and default-mode network. Furthermore, the modulations of frontolimbic alpha activity were positively correlated with the duration of meditation experience and the extent of BCI performance improvement. Overall, these data suggest that mindfulness allows participant to reach a state where they can modulate frontolimbic alpha power and improve BCI performance for SMR-based BCI control.

BACKGROUND Cavernous malformation (CM) of the subcallosal gyrus is extremely rare, and due to its close relationship with the lateral ventricle's frontal horn, it may be misdiagnosed as caudate head or ventricle CM. METHOD This video shows a rare case of subcallosal gyrus CM successfully cured by a contralateral anterior interhemispheric approach. CONCLUSION We hope this case provides new insights into anatomical knowledge and surgical approach techniques for subcallosal lesions.

The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15–35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones’ proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.

Background The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism. Methods MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to “MI group” or “No MI group.” The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis. Results The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months. Conclusions MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression. Trial registration ClinicalTrials.gov Identifier, NCT01513252.

Objective Obsessive compulsive disorder (OCD) is increasingly being recognized as a heterogeneous disorder with various symptom dimensions. In order to understand the neurobiology of obsessive-compulsive disorder (OCD), it is important to understand the brain basis of homogeneous symptom groups. In this study we investigated the gray matter (GM) changes and correlates of an exclusively homogenous sample of OCD patients (washers with no other obsessive compulsive symptoms). Method We compared the structural MRI scans (3T) using voxel-based morphometry (VBM) of washers (N = 35) with matched healthy controls (HC) (N = 39). Results We found volume deficits corresponding to right inferior frontal gyrus, parahippocampal gyrus and right anterior lobe of cerebellum among washers compared to HC. Among the washers, GM volume of right inferior frontal gyrus, right uncus of the limbic lobe, left cuneus and left superior temporal lobe had significant negative correlation with the illness severity score. Conclusion Examining homogenous sub-groups of OCD patients may help us further our understanding of neurobiology of OCD.

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime, and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. Here, we studied the neuroanatomical basis for suicide attempt history in bipolar disorder by measuring gray matter volumes (GMV) to identify differences in brain-volumes in 121 participants with bipolar disorder type I, and healthy participants (n=40). The bipolar group consisted of individuals with suicide attempt history (n=23) and no suicide attempt history (n=58). All participants completed behavioral/diagnostic assessments and MRI measures of GMV. We focused on a predefined frontolimbic circuitry in bipolar disorder versus (vs.) healthy to first identify diagnostic GMV markers and to specifically identify markers for suicide attempt history. We found reduced GMV markers for bipolar diagnosis (i.e., bipolarHighlightsSuicide is a major health problem especially in bipolar disorder but the neurobiological basis for suicide attempts remains obscure. We identified an anterior cingulate and dorsolateral prefrontal cortical volume correlate for suicide attempt history and suicidal ideation and thereby demonstrates a convergent brain marker for suicidal behaviors.

Sounds we hear in our daily life contain changes in the acoustic features (e.g., frequency, intensity, and duration or “what” information) and/or changes in location (“where” information). The purpose of this study was to examine the cortical auditory evoked potentials (CAEPs) to the change within a stimulus, the acoustic change complex (ACC), in frequency (F) and location (L) of the sound in normal hearing listeners. Fifteen right-handed young normal hearing listeners participated in the electroencephalographic (EEG) recordings. The acoustic stimuli were pure tones (base frequency at 250 Hz) of 1 sec, with a perceivable change either in location (L, 180°), frequency (F, 5% and 50%), or both location and frequency (L+F) in the middle of the tone. Additionally, the 250 Hz tone of 1 sec without any change was used as a reference. The participants were asked to listen passively to the stimuli and not to move their heads during the testing. Compared to the reference tone, by which only the onset-CAEP was elicited, the tones containing changes (L, F, or L+F) elicited both onset-CAEP and the ACC. The waveform analysis of ACCs from the vertex electrode (electrode Cz) showed that, larger sound changes evoked larger peak amplitudes [e.g., (L+50%F)- > L-change; (L+50%F)- > 5%F-change] and shorter the peak latencies ([(L+5%F)- < 5%F-change; 50%F- < 5%F-change; (L+50%F)- < 5%F-change]. The current density patterns for the ACC N1’ peak displayed some differences between L-change vs. F-change, supporting different cortical processing for “where” and “what” information of the sound; regardless of the nature of the sound change, larger changes evoked a stronger activation than smaller changes [e.g., L- > 5%F-change; (L+5%F)- > 5%F-change; 50%F- > 5%F-change] in frontal lobe regions including the cingulate gyrus, medial frontal gyrus (MFG), superior frontal gyrus (SFG), the limbic lobe cingulate gyrus, and the parietal lobe postcentral gyrus. The results suggested that sound change-detection involves memory-based acoustic comparison (the neural encoding for the sound change vs. neural encoding for the pre-change stimulus stored in memory) and involuntary attention switch.

Psychotic experiences may be understood as altered information processing due to aberrant neural computations. A prominent example of such neural computations is the computation of prediction errors (PEs), which signal the difference between expected and experienced events. Among other areas showing PE coding, hippocampal-prefrontal-striatal neurocircuits play a prominent role in information processing. Dysregulation of dopaminergic signaling, often secondary to psychosocial stress, is thought to interfere with the processing of biologically important events (such as reward prediction errors) and result in the aberrant attribution of salience to irrelevant sensory stimuli and internal representations. Bayesian hierarchical predictive coding offers a promising framework for the identification of dysfunctional neurocomputational processes and the development of a mechanistic understanding of psychotic experience. According to this framework, mismatches between prior beliefs encoded at higher levels of the cortical hierarchy and lower-level (sensory) information can also be thought of as PEs, with important consequences for belief updating. Low levels of precision in the representation of prior beliefs relative to sensory data, as well as dysfunctional interactions between prior beliefs and sensory data in an ever-changing environment, have been suggested as a general mechanism underlying psychotic experiences. Translating the promise of the Bayesian hierarchical predictive coding into patient benefit will come from integrating this framework with existing knowledge of the etiology and pathophysiology of psychosis, especially regarding hippocampal-prefrontal-striatal network function and neural mechanisms of information processing and belief updating.

Training‐induced neuroplasticity has been described in athletes' population. However, it remains largely unknown how regular training and sports proficiency modifies neuronal circuits in the human brain. In this study, we used voxel‐based morphometry and stepwise functional connectivity (SFC) analyses to uncover connectivity changes in the functional stream architecture in student‐athletes at early stages of sensorimotor skill training. Thirty‐two second‐year student‐athletes whose major was little‐ball sports and thirty‐four nonathlete controls were recruited for the study. We found that athletes showed greater gray matter volume in the right sensorimotor area, the limbic lobe, and the anterior lobe of the cerebellum. Furthermore, SFC analysis demonstrated that athletes displayed significantly smaller optimal connectivity distance from those seed regions to the dorsal attention network (DAN) and larger optimal connectivity distance to the default mode network (DMN) compared to controls. The Attention Network Test showed that the reaction time of the orienting attention subnetwork was positively correlated with SFC between the seeds and the DAN, while negatively correlated with SFC between the seeds and the DMN. Our findings suggest that neuroplastic adaptations on functional connectivity streams after motor skill training may enable novel information flow from specific areas of the cortex toward distributed networks such as the DAN and the DMN. This could potentially regulate the focus of external and internal attention synchronously in athletes, and consequently accelerate the reaction time of orienting attention in athletes.

Objectives To identify the changes of local coherence and intrinsic brain activity in resting-state idiopathic trigeminal neuralgia (ITN) patients by using regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) analysis. Methods ReHo and fALFF were analyzed in 23 ITN patients and 23 age-matched and sex-matched pain-free controls to detect the functional abnormality in the brains of ITN patients. Correlations between ReHo and fALFF were analyses. ITN pain intensity were also assessed in the ITN group. Results Compared with pain-free controls, ITN patients exhibited significantly abnormal ReHo and fALFF in several brain regions, including the cerebellum, cingulate cortex, temporal lobe, putamen, occipital lobe, limbic lobe, precuneus, insula, medial, and superior frontal gyrus compared with healthy controls. Correlation analysis showed that ReHo values of several altered brain areas positively correlated with visual analog scale values. But no correlation was found between fALFF and visual analog scale. Discussion Our results showed that ITN patients exhibited significantly abnormal spontaneous brain activity in several brain regions that are involved in pain modulation and perception. The present study reflects the maladaptive process of daily pain attacks and may enhance the understanding of how chronic pain affects local intrinsic brain activity.

OBJECTIVE This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia. DESIGN This was a cross-sectional study of 46 community-dwelling older adults, ages 70-95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function. RESULTS During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05). CONCLUSIONS Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age. TO CLAIM CME CREDITS Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive function in the clinical management of older adults at risk for dementia. LEVEL Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation and behavioral responses to emotionally stressful experiences, and chronic disruption of these systems chronically is implicated in the pathogenesis of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA activity, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Moreover, information regarding how endocrine and behavioral responses are integrated has remained obscure. Here we summarize work from our laboratory showing that anteroventral (av) bed nuclei of the stria terminalis (BST) acts as a point of convergence between the limbic forebrain and PVH, receiving and coordinating upstream influences, and restraining HPA axis output in response to inescapable stressors. Recent studies highlight a more expansive modulatory role for avBST as one that coordinates HPA-inhibitory influences while concurrently suppressing passive behavioral responses via divergent pathways. avBST is uniquely positioned to convey endocrine and behavioral alterations resulting from chronic stress exposure, such as HPA axis hyperactivity and increased passive coping strategies, that may result from synaptic reorganization in upstream limbic cortical regions. We discuss how these studies give new insights into understanding the systems-level organization of stress response circuitry, the neurobiology of coping styles, and BST circuit dysfunction in stress-related psychiatric disorders.

Objective Create a software tool to facilitate tractography-based deep brain stimulation (DBS) electrode targeting within the patient-specific stereotactic coordinate system used in the operating room. Approach: StimVision was developed with Visualization Toolkit libraries and integrates four major components: 1) medical image visualization, 2) tractography visualization, 3) DBS electrode positioning, and 4) DBS activation volume calculation with tractography intersection. Results Initial applications of StimVision are focused on the study of subcallosal cingulate (SCC) DBS for the treatment of depression. Retrospective modeling results on SCC DBS have suggested that direct stimulation of a specific collection of tractographic pathways are necessary for therapeutic benefit; thereby creating a tractography-based DBS surgical targeting hypotheses. StimVision is the tool we created to facilitate prospective clinical evaluation of that hypothesis. Significance Retrospective tractography-based analyses are common in DBS research; however, intraoperative software tools for interactive selection of a tractography-based DBS target are not readily available. StimVision provides an academic research tool to assist clinical implementation of new DBS targeting strategies and postoperative evaluation of targeting outcome.

Previous studies of trait emotional awareness (EA) have not yet examined whether differences in cortical structure might account for differences in EA. Based on previous research on the relationship between EA and both emotion conceptualization and visceromotor control processes, we tested two hypotheses in a sample of 26 healthy participants: that higher EA would be predicted by greater cortical thickness within (1) regions of the default mode network (DMN; linked with conceptualization processes), and/or (2) regions of the limbic network (linked with affect generation and visceromotor control processes). A non-significant correlation was found between EA and cortical thickness in the DMN. In contrast, a significant positive correlation was observed between EA and cortical thickness within the limbic network. These findings suggest that the structural integrity of cortical regions involved in the generation of affective bodily reactions may play a more important role in explaining differences in EA than previously thought.

Aberrant cortical-striatal-thalamic-cortical circuits have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the neurobiological basis of OCD remains unclear. We compared patterns of functional connectivity in patients with OCD and in healthy controls using resting-state magnetoencephalography (MEG). Participants comprised 24 patients with OCD (21 men, 3 women) and 22 age- and sex-matched healthy controls (19 men, 3 women). Resting-state measurements were obtained over a 6-min period using a 152-channel whole-head MEG system. We examined group differences in oscillatory activity and distribution of functional cortical hubs based on the nodal centrality of phase-locking value (PLV) maps. Differences in resting-state functional connectivity were examined through PLV analysis in selected regions of interest based on these two findings. Patients with OCD demonstrated significantly lower delta band activity in the cortical regions of the limbic lobe, insula, orbitofrontal, and temporal regions, and theta band activity in the parietal lobe regions than healthy controls. Patients with OCD exhibited fewer functional hubs in the insula and orbitofrontal cortex and additional hubs in the cingulate and temporo-parietal regions. The OCD group exhibited significantly lower phase synchronization among the insula, orbitofrontal cortex, and cortical regions of the limbic lobe in all band frequencies, except in the delta band. Altered functional networks in the resting state may be associated with the pathophysiology of OCD. These MEG findings indicate that OCD is associated with decreased functional connectivity in terms of phase synchrony, particularly in the insula, orbitofrontal cortex, and cortical regions of the limbic lobe.

Late-onset Alzheimer's disease (AD) differs substantially from early-onset AD. In this cross sectional study we investigated brain perfusion changes after 18 months of treatment with cholinesterase inhibitors (ChEIs) donepezil or galantamine. Twenty-five drug-naïve late-onset AD patients were recruited from outpatient clinics. We examined brain perfusion using single photon emission computed tomography (SPECT) and used three-dimensional stereotactic surface projection (3D-SSP) and the stereotactic extraction estimation method (SEE) level 3 to analyze classified gyrus level segments. We assessed cognitive function using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) grouped into three subgroup domains, language, memory, and praxis. In the follow-up data, some regions were further hypoperfused, reflecting worsening of the disease, while other regions showed alleviated hypoperfusion, potentially related to the ChEIs treatment. Regional cerebral blood flow (rCBF) decreased in the parietal cortex and increased in the frontal and the limbic cortices. Increased hypoperfusion significantly correlated with ADAS-cog scores changes were seen in the superior parietal lobule, inferior parietal lobule, angular gyrus, and supramarginal gyrus of the parietal cortex. Alleviated hypoperfusion significantly related to recovery of ADAS-cog scores were seen in the rectal and paracentral lobule of the frontal cortex, and the anterior cingulate of the limbic cortex. These regions showed significant relationships with total ADAS-cog and language, memory and praxis subscales scores. The current longitudinal study indicates prominent rCBF changes and their relationships with changes in ADAS-cog scores in late-onset AD patients.

Previous studies have demonstrated that alterations of gray matter exist in post-stroke aphasia (PSA) patients. However, so far, few studies combined structural alterations of gray matter volume (GMV) and intrinsic functional connectivity (iFC) imbalances of resting-state functional MRI to investigate the mechanism underlying PSA. The present study investigated specific regions with GMV abnormality in patients with PSA (n = 17) and age- and sex- matched healthy controls (HCs, n = 20) using voxel-based morphometry. In addition, we examined whether there is a link between abnormal gray matter and altered iFC. Furthermore, we explored the correlations between abnormal iFC and clinical scores in aphasic patients. We found significantly increased GMV in the right superior temporal gyrus, right inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and left middle occipital gyrus. Decreased GMV was found in the right caudate gyrus, bilateral thalami in PSA patients. Patients showed increased remote interregional FC between the right IPL/SMG and right precuneus, right angular gyrus, right superior occipital gyrus; while reduced FC in the right caudate gyrus and supplementary motor area, dorsolateral superior frontal gyrus. Moreover, iFC strength between the left middle occipital gyrus and the left orbital middle frontal gyrus was positively correlated with the performance quotient. We suggest that GMV abnormality contributes to interregional FC in PSA. These results may provide useful information to understand the pathogenesis of post-stroke aphasia.

Objective To analyze changes in cerebral grey matter volume and white matter density in non-dementia Parkinson’s disease patients using voxel-based morphometry (VBM) technology; to investigate features of brain structure changes in Parkinson’s disease patients with mild cognitive impairment (PD-MCI), and reveal their intrinsic pathological changes. Methods Based on the diagnostic criteria of PD-MCI, 23 PD-MCI patients, 23 Parkinson’s disease patients with normal cognition (PD-NC), and 21 age- and gender-matched healthy people were recruited for the study. Scans were performed on all subjects on a 3.0T MR scanner to obtain brain structural magnetic resonance images. Images were preprocessed using the VBM8 tool from SPM8 software package on the Matlab R2008a platform, and data were then analyzed using the SPM statistical software package to compare the differences of grey matter volume and white matter density between groups, and to evaluate the brain structural changes corresponding to the overall cognitive function. Results Compared to the control group, the PD-NC group suffered from grey matter atrophy, mainly found in the prefrontal lobe, limbic lobe and left temporal gyrus. The PD-MCI group suffered from grey matter atrophy found in the frontal lobe, limbic lobe, basal ganglia and cerebellum. Compared to the PD-NC group, the PD-MCI group suffered from grey matter atrophy found in the left-side middle temporal gyrus, inferior temporal gyrus and frontal lobe. The grey matter regions correlated with MMSE score (mainly memory related) including the right cingulate gyrus and the limbic lobe. The grey matter regions correlated with MoCA score (mainly non-memory related) including the frontal lobe, basal ganglia, parahippocampal gyrus, occipital lobe and the cerebellum. Additionally, overall cognitive function in non-dementia PD was mainly located in the frontal and limbic system, and was dominated by subcortical atrophy. Conclusion Structural changes in PD-MCI patients are associated with overall cognitive function, and the atrophic areas are mainly located in the frontal and limbic system, and are dominated by subcortical atrophy. Moreover, atrophy of limbic lobes is associated with impaired memory, whereas frontal lobe atrophy is associated with executive dysfunction. In addition, the subtle brain structure of the PD early cognitive impairment stage and PD-MCI stage can be detected via VBM technology, and thus, local brain atrophy may be a neuroimaging marker for the early diagnosis of PD-MCI.

Middle childhood is an important period for individual trait shaping, during which children are likely to generate and own their distinct neuromechanism of creative-related traits. This study used voxel-based morphometry (VBM) to identify the brain structures that underlie trait creativity (as measured by the Williams Creativity Aptitude Test) in a sample of typical developing children (aged 9–12, n = 64). The results indicated that several emotion-related regions may relate to trait creativity in middle children. Specifically, the regional gray matter volume (rGMV) in the amygdala and hippocampus was negatively related to creative traits of challenge and risk-taking, which indicates that children with increased trait creativity may be more impulsive when they engage in creative activities. An increased rGMV in the orbitofrontal cortex (OFC) was related to an increased trait of imagination, which may be associated with stronger sensation-seeking in children. These findings are the first to demonstrate the brain structures that underlie trait creativity in middle children, and indicated that, driven by a relatively stronger effect of sensation-seeking (via recruitment of the OFC), children with increased trait creativity may exhibit more risk-taking and challenging behaviors (via recruitment of the amygdala and hippocampus) when they practice their creativity.

It has been reported that chronic heroin intake induces both structural and functional changes in human brain; however, few studies have investigated the carry-over adverse effects on brain after heroin withdrawal. In this paper, we examined the neurophysiological differences between the abstinent heroin addicts (AHAs) and healthy controls (HCs) using nonlinear dynamic analysis and source localization analysis in resting-state electroencephalogram (EEG) data; 5 min resting EEG data from 20 AHAs and twenty age-, education-, and gender-matched HCs were recorded using 64 electrodes. The results of nonlinear characteristics (e.g., the correlation dimension, Kolmogorov entropy, and Lempel-Ziv complexity) showed that the EEG signals in alpha band from AHAs were significantly more irregular. Moreover, the source localization results confirmed the neuronal activities in alpha band in AHAs were significantly weaker in parietal lobe (BA3 and BA7), frontal lobe (BA4 and BA6), and limbic lobe (BA24). Together, our analysis at both the sensor level and source level suggested the functional abnormalities in the brain during heroin abstinence, in particular for the neuronal oscillations in alpha band.

Alterations of the topological organization of abnormal regions or network-level structural aberrations are still poorly understood for post-traumatic stress disorder (PTSD). Herein, we investigated brain structural networks in recent-onset PTSD patients, all affected by the coalmine-flood disaster. Cortical networks were studied in recent onset PTSD patients (n = 15) and matched healthy controls (n = 25). Cortical networks were constructed by thresholding correlation matrices of 150 regions and quantified using graph theoretical approaches. Contributions of high-degree nodes, and regional and global network measures, including degree and betweenness, were studied. Compared with healthy controls, PTSD patients showed altered quantitative values in global network properties, characterized by shorter path length and higher clustering. Moreover, PTSD patients exhibited decreased connectivity in the right lingual gyrus, parahippocampal gyrus, left supramarginal gyrus, parahippocampal gyrus, bilateral superior and inferior frontal gyrus, superior frontal gyrus, and posterior cingulate gyrus. Nodal centrality decreased predominantly in the occipital regions (lingual gyrus) and default-mode regions, while increased correlations and centralities were observed in the medial temporal lobe and posterior cingulate cortex. PTSD-related networks exhibited a less efficient organization and regional connectivity. According to these findings, we conclude that regional connections involving fear-processing and re-experiential-processing cortex may play a role in maintaining or adapting to PTSD pathology.

Touch, such as affective caress, can be interpreted as being pleasant. The emotional valence that is assigned to touch is related to certain bottom-up factors, such as the optimal activation of C-tactile (CT) afferents. Tactile processing with a hedonic or emotional component has been defined as affective touch—a component that CT fibers are likely to convey. Tactile deficiencies are frequent in the psychiatric population but also in healthy people with disorganized attachment; accordingly, it is likely that affective difficulties in adults with disorganized attachment are reflected in altered perception of affective touch. To test this hypothesis, we combined methods from clinical psychology, psychophysics, and neuroimaging. We found that people with a history of traumatic parental bonds and a disorganized attachment pattern perceive a “caress-like” stimulus as being unpleasant, whereas participants with organized attachment consider the same tactile stimulation to be pleasant. Further, unlike in organized adults, the responses of disorganized adults to CT and non-CT stimulation activated limbic and paralimbic structures in a fight-or-flight manner, suggesting that early experiences with parental deficiencies shape the physiological responses of peripheral CT fibers and central nervous networks.

Background: Pregnancy constitutes a significant period in the lives of women, after which they often experience numerous crucial physiological and psychological changes. Functional neuroimaging studies have shown longitudinal changes in functional brain activity in mothers responding to infant-related stimuli. However, the structural changes that occur in the brains of mothers after delivery remain to be explored. Objective: We aimed to evaluate the structural changes in mothers during the postpartum phase. Methods: We recruited 35 primiparous mothers and 26 nonmothers to participate in this voxel- and surface-based morphometry study, and 22 mothers were scanned twice with a follow-up of approximately 2 years. Results: Compared to nonmothers, mothers exhibited reduced gray matter (GM) volumes and increased white matter (WM) volumes in regions associated with empathy and reward networks (supplementary motor area, precuneus, inferior parietal lobe, insula, and striatum), decreased cortical thickness in the precentral gyrus and increased gyrification index in the orbitofrontal cortex. Furthermore, mothers showed longitudinal changes in the GM and WM volumes and cortical thickness of several of these regions (including the superior and medial frontal gyrus, insula, limbic lobe, superior and middle temporal gyrus, and precentral gyrus), which have been associated with maternal networks during the postpartum period. Additionally, the changes in GM and WM volumes were related to changes in empathetic abilities in mothers. Conclusion: These results suggest that the brains of mothers exhibit adaptive structural dynamic plasticity. These findings provide a neuroanatomical basis for understanding how mothers process emotional sensory information during the postpartum period.

BACKGROUND AND OBJECTIVES: Cushing’s disease (CD) patients have metabolic abnormalities in the brain caused by excessive exposure to endogenous cortisol. However, the reversibility of brain metabolism of CD patients after treatment remains largely unknown. METHODS: This study recruited 50 CD patients seeking treatment and 34 matched normal controls (NCs). The patients were treated with Transsphenoidal Adenomectomy (TSA) and reexamined 3 months later. Cerebral blood flow (CBF) of the patients were assessed using 3D pseudo-continuous arterial spin labelling (PCASL) imaging before the treatment and at the 3-month follow-up and were compared with CBF measures of the NCs using a whole-brain voxelwise group comparison method. For remitted patients, their CBF measures and hormone level measures, including adrenocorticotropic hormone (ACTH), 24-hour urinary free cortisol (24hUFC) and serum cortisol, were compared before and after the treatment. Finally, a correlation analysis was carried out to explore the relationship between changes of CBF and hormone level measures of the remitted CD patients. RESULTS: After the treatment, 45 patients reached remission. Compared with the NCs, the CD patients before the treatment exhibited significantly reduced CBF in cortical regions, including occipital lobe, parietal lobe, superior/middle/inferior temporal gyrus, superior/middle/inferior frontal gyrus, orbitofrontal cortex, precentral gyrus, middle/posterior cingulate gyrus, and rolandic operculum, as well as significantly increased CBF in subcortical structures, including caudate, pallidum, putamen, limbic lobe, parahippocampal gyrus, hippocampus, thalamus, and amygdala (p

ObjectivesDeep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by (i) developing a structural MRI approach for CM visualisation, (ii) identifying the CM’s neurophysiological characteristics, and (iii) mapping connectivity from CM-DBS sites using functional MRI (fMRI).MethodsNineteen patients with LGS (mean age=28 years) underwent pre-surgical 3 tesla MRI using magnetisation-prepared 2 rapid acquisition gradient echoes (MP2RAGE) and fMRI sequences; 16 proceeded to bilateral CM-DBS implantation and intraoperative microelectrode recordings (MERs) from the thalamus. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge-detection. Mixed-effects analysis compared two MER features (spike firing rate, background noise) between ventrolateral, CM, and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions-of-interest.ResultsThe CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal, and parafasicular nuclei. At the group-level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex.ConclusionsIn the largest clinical trial cohort of LGS patients undergoing CM-DBS reported to date, we show that accurate targeting of the CM is achievable using 3 tesla MP2RAGE MRI. MERs may provide additional localising features in some cases, however their utility is limited by inter-patient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive, and sensorimotor processes.

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement (‘None-Go’ task, n = 7, 28 recording sites); second, pressing a button after every tone (‘All-Go’ task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones (‘Go-NoGo’ task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation.

Olfactory function, and specifically semantic olfactory memory (i.e., odor identification), has frequently been shown to predict cognitive functioning across multiple domains in old age. This observation suggests that olfactory function can serve as a marker for the integrity of temporolimbic cortical networks, but a clear delineation of this association is still missing. To address this issue, the present study employed voxel-based morphometry in a region of interest-based design to determine the extent to which gray matter volumes of core olfactory and memory areas are associated with olfactory memory performance in an aging population free from neurodegenerative disease. We further aimed to determine potential overlap in structural anatomical correlates, and differences in association strength, for semantic and episodic olfactory memory. Structural magnetic resonance imaging (MRI), episodic and semantic odor memory and episodic and semantic verbal memory data were collected in 422 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), all aged ​≥ ​60 years. Controlling for age and education, semantic, but not episodic, olfactory memory was positively related to gray matter volume in a cluster extending from the anterior hippocampus and amygdala into the posterior piriform cortex. The observed associations remained even when verbal memory performance was controlled for, supporting a link between the olfactory memory domain and cortical volume over and above more generalized memory abilities. As such, our data provide evidence for distinct functional-structural associations for semantic odor memory, supporting the idea of temporolimbic integrity as a neurobiological substrate linking olfactory function to cognitive health in old age.

Background: Comorbid anxious distress is common in Major Depressive Disorder (MDD), and associated with significantly worse clinical course and treatment response. While DSM-5 recently introduced the Anxious Distress (AD) specifier as a potentially useful symptom-based subtyping scheme for MDD, its neurobiological underpinnings remain unclear. The current study hence uniquely probed whether MDD with co-occurring AD (MDD/AD+) relates to distinct perturbations in frontolimbic white matter (WM) pathways tentatively theorized in MDD/AD+ pathophysiology.Methods: Tract-based spatial statistics (TBSS) was therefore used to analyze diffusion tensor imaging data on WM microstructure, in MDD/AD+ patients (N = 20) relative to MDD patients without AD (MDD/AD-; N = 29) and healthy controls (HC; N = 39). Using TBSS, we probed fractional anisotropy and axial/radial/mean diffusivity as proxies for WM integrity. Categorical (between-groups) and dimensional (within-patients) analyses subsequently assessed how Anxious Distress in MDD impacts frontolimbic WM connectivity. Receiver-Operating Characteristics additionally assessed classification capabilities of between-groups WM effects.Results: Compared to MDD/AD- and HC participants, MDD/AD+ patients exhibited diminished integrity within the anterior thalamic radiation (ATR). Higher AD specifier scores within MDD patients additionally related to diminished integrity of the uncinate fasciculus and cingulum pathways. These effects were not confounded by key clinical (e.g., comorbid anxiety disorder) and sociodemographic (e.g., age/sex) factors, with altered ATR integrity moreover successfully classifying MDD/AD+ patients from MDD/AD- and HC participants (90% sensitivity vertical bar 73% specificity vertical bar 77% accuracy).Conclusions: These findings collectively link MDD/AD+ to distinct WM anomalies in frontolimbic tracts important to adaptive emotional functioning, and may as such provide relevant, yet preliminary, clues on MDD/AD+ pathophysiology.

Mild cognitive impairment (MCI) is commonly observed in Parkinson’s disease (PD), even in the early stages. However, the neural substrates of cognitive impairment in PD remain unclear. The aim of the current study was to investigate the change of local brain function in PD patients with MCI. Fifty patients with PD, including 25 PD patients with MCI (PD-MCI) and 25 PD patients with normal cognition (PD-NC), and 25 age- and sex-matched healthy controls (HC) were enrolled. Conventional magnetic resonance imaging (MRI), 3D structural images, and resting state-functional MRI (rs-fMRI) were performed in all subjects. Regional homogeneity (ReHo) was measured based on the rs-fMRI images to investigate the altered local brain functions. Brain regions with decreased ReHo were located in the left posterior cerebellar lobe in PD sub-groups compared to the HC group, and the brain regions with increased ReHo were located in the limbic lobe (right precuneus/bilateral middle cingulate cortex) in PD-MCI compared with HC group. PD-MCI presented with increased ReHo in the bilateral precuneus/left superior parietal lobe and decreased ReHo in the left insula compared to PD-NC. ReHo values for the left precuneus were negatively related to neuropsychological scores, and ReHo values for the left insula were positively related to neuropsychological scores in PD subjects. The present study demonstrated abnormal spontaneous synchrony in the left insula and left precuneus in patients with PD-MCI compared to PD-NC, which might provide a novel insight into the diagnosis and clinical treatment of cognitive impairment in PD.