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Background: Pain thresholds and primary headaches, including cluster headache attacks, have circadian rhythmicity. Thus, they might share a common neuronal mechanism. Objective: This study aimed to elucidate how the modulation of nociceptive input in the brainstem changes from noon to midnight. Insights into the mechanism of these fluctuations could allow for new hypotheses about the pathophysiology of cluster headache. Methods: This repeated measure observational study was conducted at the University Hospital Zurich from December 2019 to November 2022. Healthy adults between 18 and 85 years of age were eligible. All participants were examined at noon and midnight. We tested the pain threshold on both sides of the foreheads with quantitative sensory testing, assessed tiredness levels, and obtained high‐field (7 Tesla) and high‐resolution functional magnetic resonance imaging (MRI) at each visit. Functional connectivity was assessed at the two visits by performing a region‐of‐interest analysis. We defined nuclei in the brainstem implicated in processing nociceptive input as well as the thalamus and suprachiasmatic nucleus as the region‐of‐interest. Results: Ten people were enrolled, and seven participants were included. First, we did not find statistically significant differences between noon and midnight of A‐delta‐mediated pain thresholds (median mechanical pain threshold at noon: left 9.2, right 9.2; at night: left 6.5, right 6.1). Second, after correction for a false discovery rate, we found changes in the mechanical pain sensitivity to have a statistically significant effect on changes in the functional connectivity between the left parabrachial nucleus and the suprachiasmatic nucleus (T = −40.79). Conclusion: The MRI data analysis suggested that brain stem nuclei and the hypothalamus modulate A‐delta‐mediated pain perception; however, these changes in pain perception did not lead to statistically significantly differing pain thresholds between noon and midnight. Hence, our findings shed doubt on our hypothesis that the physiologic circadian rhythmicity of pain thresholds could drive the circadian rhythmicity of cluster headache attacks. Plain Language Summary: We wanted to find out if cluster headache attacks occur primarily at night because even healthy persons are more likely to feel pain at that time. Our sample of healthy participants did not have lower pain thresholds in the evening than at noon, and brain imaging suggested that the measurements were accurate. Thus, we could not prove our idea. [ABSTRACT FROM AUTHOR]

Background: This study aimed to provide an up-to-date account of the frequency of "the absence of interthalamic adhesion (AITA) as a risk factor or association" in healthy subjects and neuropsychiatric patients. Owing to the increased interest in the contribution of ITA to neurological function in previous literature, a meta-analysis of its frequency and sex dependency is required. Aim: This study aimed to study whether the AITA is associated with neuropsychiatric disorders. Settings and Design: This study is a meta-analysis and systemic review. Methods and Material: Literature searches were conducted in PubMed, Web of Science, and Google Scholar using the keywords "interthalamic adhesion," "massa intermedia," "adhesio interthalamica," and "adhesion" along with the Boolean operators (OR, AND, and NOT). Three reviewers independently assessed the abstracts and full texts for validation based on the inclusion criteria. The meta-analysis was performed using Microsoft Excel 2019 for descriptive studies and RevMan 5.2 for comparative studies. Results: The incidence of absent ITA was 15.3% in healthy subjects and 28.76% in neuropsychiatric subjects. The relative probability of AITA was 2.30 [95% confidence interval (CI), 1.96-2.70] in neuropsychiatric illness. Healthy men were 1.91 times more likely, and men with neuropsychiatric disorders were 1.82 times more likely to have absent ITA than women. Conclusions and Relevance: In this study, a consistent association of AITA with psychiatric disorders was observed, rendering the condition to be treated as an associated risk factor affecting the function of the habenula nuclear complex via the stria medullaris thalami. A cohort or longitudinal study is needed to compare the incidence of psychiatric disorders in individuals with or without ITA and to calculate the attributed risk. [ABSTRACT FROM AUTHOR]

Background: The trigeminal vascular system is an important part of the anatomical and physiological basis of migraine. The effective connectivity (EC) among the regions of interest (ROIs) in the trigeminal vascular system involved in migraine without aura (MWoA) remains unclear. Methods: In this cross‐sectional study, 48 patients (mean [SD] age 38.06 [10.35] years; male, 14/48 [29%]) with MWoA during the interictal phase and 48 healthy controls of similar age and sex (mean [SD] age 38.96 [10.96] years; male, 14/48 [29%]) underwent resting‐state functional magnetic resonance imaging (fMRI). Dynamic causal modeling analysis was conducted to investigate directional EC among ROIs in the trigeminal vascular system including the bilateral brainstem, the primary somatosensory cortex (S1), the thalamus, and the insula. Results: Compared with the healthy control group, MWoA represented significantly reduced EC from the left brainstem (Brainstem.L) to the left insula (MWoA: mean [SD] −0.16 [0.36]; healthy controls: mean [SD] 0.11 [0.41]; Pcorrected = 0.021), reduced EC from the Brainstem.L to the right insula (MWoA: mean [SD] −0.15 [0.39]; healthy controls: mean [SD] 0.03 [0.35]; Pcorrected = 0.021), and decreased EC from the left thalamus (Thalamus.L) to the Brainstem.L (MWoA: mean [SD] −0.13 [0.56]; healthy controls: mean [SD] 0.10 [0.45]; Pcorrected = 0.021). Altered EC parameters were not significantly correlated with MWoA clinical data. Conclusion: These results further provide increasing evidence that disturbed homeostasis of the trigeminovascular nociceptive pathway is involved in the pathophysiological mechanisms of migraine. Patients with MWoA exhibited a regional interaction distinct from healthy controls in the neural pathway of the Bilateral Insula–Brainstem.L–Thalamus.L, which may shed light on the future understanding of brain mechanisms for MWoA. Future brain‐based interventions are suggested to consider the dysregulation in the Bilateral Insula–Brainstem.L–Thalamus.L circuits. [ABSTRACT FROM AUTHOR]

Global Developmental Delay (GDD) and Intellectual Disability (ID) are two of the most common presentations encountered by physicians taking care of children. GDD/ID is classified into non-syndromic GDD/ID, where GDD/ID is the sole evident clinical feature, or syndromic GDD/ID, where there are additional clinical features or co-morbidities present. Careful evaluation of children with GDD and ID, starting with detailed history followed by a thorough examination, remain the cornerstone for etiologic diagnosis. However, when initial history and examination fail to identify a probable underlying etiology, further genetic testing is warranted. In recent years, genetic testing has been shown to be the single most important diagnostic modality for clinicians evaluating children with non-syndromic GDD/ID. In this review, we discuss different genetic testing currently available, review common underlying copy-number variants and molecular pathways, explore the recent evidence and recommendations for genetic evaluation and discuss an approach to the diagnosis and management of children with non-syndromic GDD and ID. [ABSTRACT FROM AUTHOR]

Paroxysmal kinesigenic dyskinesia (PKD) is a kind of nervous system disease characterized by paroxysmal involuntary movements induced by sudden movements. Neuroimaging studies have found that there are structural changes or abnormal functional connectivity in the basal ganglia, thalamus, cortex and other brain regions in PKD patients. The weakened inhibitory and regulatory function of the basal ganglia to the thalamus or the dysfunction of the thalamus itself may cause over-activation of the cortical region, resulting in involuntary movements. Recent studies have found that abnormal cerebellar function plays an important role in the pathogenesis of PKD, and abnormal cerebellar cortex can affect its normal inhibitory effect on deep cerebellar nuclei, also leading to excessive activation of thalamic - cortical pathway. This paper reviewed the mechanism and research progress of PKD in recent years, mainly focusing on the basal ganglia-thalamic-cortical circuit and the cerebellar-thalamic-cortical circuit, so as to improve clinicians' understanding of the pathogenesis of movement disorders. [ABSTRACT FROM AUTHOR]

Background: Post-operative delirium (POD), a common post-operative complication that aects up to 73. 5% of surgical patients, could prolong hospital stays, triple mortality rates, cause long-term cognitive decline and dementia, and boost medical expenses. However, the underlying mechanisms, especially the circuit mechanisms of POD remain largely unclear. Previous studies demonstrated that cannabis use might cause delirium-like behavior through the endocannabinoid system (eCBs), a widely distributed retrograde presynaptic neuromodulator system. We also found that the prelimbic (PrL) and intralimbic (IL) prefrontal cortex, a crucial hub for cognition and emotion, was involved in the eCBs-associated general anesthesia recovery. Objectives: The present study aimed to investigate the role of eCBs in POD development, and further clarify its neuronal specificity and circuit specificity attributed to POD. Methods: According to a previous study, 2 h of 1.4% isoflurane anesthesia and simple laparotomy were conducted to establish the POD model in C57/BL6 mice aged 8–12 weeks. A battery of behavioral tests, including the buried food, open field, and Y maze tests, were performed at 24 h before anesthesia and surgery (AS) and 6 and 9 h after AS. The behavioral results were calculated as a composite Z score for the POD assessment. To explore the dynamics of eCBs and their eect on POD regulation, an endocannabinoid (eCB) sensor was microinjected into the PrL, and the antagonists (AM281 and hemopressin) and agonist (nabilone) of type 1 cannabinoid receptor (CB1R), were administered systemically or locally (into PrL). Chemogenetics, combined Cre-loxP and Flp-FRT system, were employed in mutant mice for neuronal specificity and circuit specificity observation. Results: After AS, the composite Z score significantly increased at 6 and 9 but not at 24 h, whereas blockade of CB1R systemically and intra-PrL could specifically decrease the composite Z score at 6 and 9 h after AS. Results of fiber photometry further confirmed that the activity of eCB in the PrL was enhanced by AS, especially in the Y maze test at 6 h post-operatively. Moreove the activation of glutamatergic neurons in the PrL could reduce the composite Z score, which could be significantly reversed by exogenous cannabinoid (nabilone) at 6 and 9 h post-operatively. However, activation of GABAergic neurons only decreased composite Z score at 9 h post-operatively, with no response to nabilone application. Further study revealed the glutamatergic projection from mediodorsal thalamus (MD) to PrL glutamatergic neurons, but not hippocampus (HIP)-PrL circuit, was in charge of the eect of eCBs on POD. Conclusion: Our study firstly demonstrated the involvement of eCBs in the POD pathogenesis and further revealed that the eCBs may regulate POD through the specific MDglu-PrLglu circuit. These findings not only partly revealed the molecular and circuit mechanisms of POD, but also provided an applicable candidate for the clinical prevention and treatment of POD. [ABSTRACT FROM AUTHOR]

Background: The thalamus plays a crucial role in transmitting nociceptive information to various cortical regions involving migraine-related allodynia and photophobia. Abnormal structural and functional alterations related to the thalamus have been well established. However, it is unknown whether the brain structure and function of the thalamic subregions are differentially affected in this disorder. In this study, we aimed to clarify this issue by comparing the structure and function of 16 thalamic subregions between patients with episodic migraine (EM) and healthy controls (HCs). Methods: Twenty-seven patients with EM and 30 sex-, age- and education-matched HCs underwent resting-state functional and structural magnetic resonance imaging scans. Functional connectivity (rsFC), grey matter volume (GMV), and diffusion tensor imaging (DTI) parameters of each subregion of the thalamus were calculated and compared between the two groups. Furthermore, correlation analyses between neuroimaging changes and clinical features were performed in this study. Results: First, compared with HCs, patients with EM exhibited decreased rsFC between the anterior-medial-posterior subregions of the thalamus and brain regions mainly involved in the medial system of the pain processing pathway and default mode network (DMN). Second, for the whole thalamus and each of its subregions, there were no significant differences in GMV between patients with EM and HCs (P > 0.05, Bonferroni corrected). Third, there was no significant difference in DTI parameters between the two groups (P > 0.05). Finally, decreased rsFC was closely related to scores on the Hamilton Rating Scale for Anxiety (HAMA) and Big Five Inventory (BFI) scales. Conclusion: Selective functional hypoconnectivity in the thalamic subregions provides neuroimaging evidence supporting the important role of thalamocortical pathway dysfunction in episodic migraine, specifically, that it may modulate emotion and different personality traits in migraine patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the alterations of thalamic nuclei volumes and the intrinsic thalamic network in patients with cluster headache and healthy controls. Methods: We retrospectively enrolled 24 patients with episodic cluster headache and 24 healthy controls. We calculated the thalamic nuclei volumes in the patients with cluster headache and healthy controls based on three-dimensional T1-weighted imaging with automated segmentation using the FreeSurfer program. We also investigated the intrinsic thalamic network using structural co-variance analysis based on the thalamic nuclei volumes and graph theory under the BRAPH program. We compared the thalamic nuclei volumes and intrinsic thalamic networks in patients with cluster headaches and healthy controls. Results: The right and left whole thalamic volumes did not differ in the patients with cluster headaches and healthy controls (0.4199 vs. 0.4069%, p = 0.2008; 0.4386 vs. 0.4273%, p = 0.3437; respectively). However, there were significant alterations of right and left medial geniculate nuclei volumes in the patients with cluster headaches and the healthy controls. The right and left medial geniculate nuclei volumes of the patients with cluster headaches were greater than those of the healthy controls (0.0088 vs. 0.0075%, p < 0.0001; 0.0086 vs. 0.0072%, p < 0.0001; respectively). The intrinsic thalamic networks of the groups were not different. Conclusion: This study demonstrates significant alterations in the bilateral medial geniculate nuclei volumes in patients with cluster headache compared to healthy controls. These alterations may be related to the pathophysiology of cluster headache. However, there are no changes in the intrinsic thalamic network in patients with cluster headache. [ABSTRACT FROM AUTHOR]

Diabetes can damage both the peripheral sensory organs, causing retinopathy, and the central visual system, leading to contrast sensitivity and impaired color vision in patients without retinopathy. Orientation discrimination is important for shape recognition by the visual system. Our psychophysical findings in this study show diminished orientation discrimination in patients with diabetes without retinopathy. To reveal the underlying mechanism, we established a diabetic mouse model and recorded in vivo electrophysiological data in the dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (V1). Reduced orientation selectivity was observed in both individual and populations of neurons in V1 and dLGN, which increased in severity with disease duration. This diabetes-associated neuronal dysfunction appeared earlier in the V1 than dLGN. Additionally, neuronal activity and signal-to-noise ratio are reduced in V1 neurons of diabetic mice, leading to a decreased capacity for information processing by V1 neurons. Notably, the V1 in diabetic mice exhibits reduced excitatory neuronal activity and lower levels of phosphorylated mammalian target of rapamycin (mTOR). Our findings show that altered responses of both populations of and single V1 neurons may impair fine vision, thus expanding our understanding of the underlying causes of diabetes-related impairment of the central nervous system. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence has shown that amyotrophic lateral sclerosis (ALS) can result in abnormal energy metabolism and sleep disorders, even before motor dysfunction. Although the hypothalamus and thalamus are important structures in these processes, few ALS studies have reported abnormal MRI structural findings in the hypothalamus and thalamus. Purpose: We aimed to investigate volumetric changes in the thalamus and hypothalamus by using the automatic brain structure volumetry tool AccuBrain®. Methods: 3D T1-weighted magnetization-prepared gradient echo imaging (MPRAGE) scans were acquired from 16 patients with ALS with normal cognitive scores and 16 age-, sex- and education-matched healthy controls. Brain tissue and structure volumes were automatically calculated using AccuBrain®. Results: There were no significant differences in bilateral thalamic (F = 1.31, p = 0.287) or hypothalamic volumes (F = 1.65, p = 0.213) between the ALS and control groups by multivariate analysis of covariance (MANCOVA). Left and right hypothalamic volumes were correlated with whole-brain volume in patients with ALS (t = 3.19, p = 0.036; t = 3.03, p = 0.044), while the correlation between age and bilateral thalamic volumes tended to be significant after Bonferroni correction (t = 2.76, p = 0.068; t = 2.83, p = 0.06). In the control group, left and right thalamic volumes were correlated with whole-brain volume (t = 4.26, p = 0.004; t = 4.52, p = 0.004). Conclusion: Thalamic and hypothalamic volumes did not show differences between patients with normal frontotemporal function ALS and healthy controls, but further studies are still needed. [ABSTRACT FROM AUTHOR]

Background Thalamocortical circuit imbalance characterized by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity has been consistently documented at rest in schizophrenia (SCZ). However, this thalamocortical imbalance has not been studied during task engagement to date, limiting our understanding of its role in cognitive dysfunction in schizophrenia. Methods Both n-back working memory (WM) task-fMRI and resting-state fMRI data were collected from 172 patients with SCZ and 103 healthy control subjects (HC). A replication sample with 49 SCZ and 48 HC was independently obtained. Sixteen thalamic subdivisions were employed as seeds for the analysis. Results During both task-performance and rest, SCZ showed thalamic hyperconnectivity with sensorimotor cortices, but hypoconnectivity with prefrontal-cerebellar regions relative to controls. Higher sensorimotor-thalamic connectivity and lower prefronto-thalamic connectivity both relate to poorer WM performance (lower task accuracy and longer response time) and difficulties in discriminating target from nontarget (lower d′ score) in n-back task. The prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity were anti-correlated both in SCZ and HCs; this anti-correlation was more pronounced with less cognitive demand (rest>0-back>2-back). These findings replicated well in the second sample. Finally, the hypo- and hyper-connectivity patterns during resting-state positively correlated with the hypo- and hyper-connectivity during 2-back task-state in SCZ respectively. Conclusions The thalamocortical imbalance reflected by prefronto-thalamic hypoconnectivity and sensorimotor-thalamic hyperconnectivity is present both at rest and during task engagement in SCZ and relates to working memory performance. The frontal reduction, sensorimotor enhancement pattern of thalamocortical imbalance is a state-invariant feature of SCZ that affects a core cognitive function. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been successful in mitigating upper limb tremor, but the effect on gait and balance performance is unclear. Here, we aim to examine the effectiveness of VIM DBS on stride length variability, sway path length, and task-relevant tremor of various body segments in essential tremor (ET). Methods: Seventeen ET individuals treated with DBS (ET DBS) and 17 age-and sexmatched healthy controls (HC) performed a postural balance and overground walking task. In separate and consecutive visits, ET DBS performed gait and balance tasks with DBS ON or OFF. The main outcome measures were sway path length, stride length variability, and tremor quantified from upper limb, lower limb, upper and lower trunk (axial) during the gait and balance tasks. Results: With DBS OFF, ET DBS exhibited significantly greater stride length variability, sway path length, and tremor during gait and balance task relative to HC. Relative to DBS OFF, DBS ON reduced stride length variability and sway path length in ET DBS. The DBS-induced reduction in stride length variability was associated with the reduction in both upper trunk tremor and upper limb tremor. The DBS-induced reduction in sway path length was associated with the reduction in upper trunk tremor. Discussion: The findings of this study revealed that VIM DBS was effective in improving gait and balance in ET DBS and that improvements in gait and postural balance were associated with a reduction of axial tremor during the tasks. [ABSTRACT FROM AUTHOR]

Study Objectives: Sleep spindles play a crucial role in multiple neuronal network functions. Initiation and termination of spindles are regulated by the thalamic reticular nucleus and thalamocortical network, and the spindle can be an index for brain organization. We conducted a preliminary study of the parameters of sleep spindles, focusing on sleep-stage temporal distribution in children with autism spectrum disorder (ASD) with normal intelligence/developmental quotients. Methods: We performed overnight polysomnography in 14 children with ASD (4-10 years) with normal full-scale intelligence quotient/developmental quotient (≥75) and 14 community samples (CS) of children. Sleep stages were scored according to the Rechtschaffen and Kales criteria. Spindle parameters were quantified and compared between these groups and the identified subgroups. Results: Sleep parameters did not differ between the ASD and CS groups, except for a higher rate of rapid eye movement (REM) sleep duration in ASD. Spindle parameters did not significantly differ between the groups, but spindle density was distributed in a broader range in the ASD group. Five children with ASD had a higher spindle density in stage 3 than in stage 2. The ratio of spindle density in stage 3 to that in stage 2 (stage 3/2 ratio) was significantly higher in ASD than in CS cases. Conclusions: The lower spindle density in stage 2 and relatively higher density in stage 3 in children with ASD may represent an abnormal generation of spindles due to insufficient maturation of the thalamic reticular nucleus and thalamocortical network. [ABSTRACT FROM AUTHOR]

Background: One hypothesis proposed to underlie formal thought disorder (FTD), the incoherent speech is seen in some patients with schizophrenia, is that it reflects impairment in frontal/executive function. While this proposal has received support in neuropsychological studies, it has been relatively little tested using functional imaging. This study aimed to examine brain activations associated with FTD, and its two main factor-analytically derived subsyndromes, during the performance of a working memory task. Methods: Seventy patients with schizophrenia showing a full range of FTD scores and 70 matched healthy controls underwent fMRI during the performance of the 2-back version of the n-back task. Whole-brain corrected, voxel-based correlations with FTD scores were examined in the patient group. Results: During 2-back performance the patients showed clusters of significant inverse correlation with FTD scores in the inferior frontal cortex and dorsolateral prefrontal cortex bilaterally, the left temporal cortex and subcortically in the basal ganglia and thalamus. Further analysis revealed that these correlations reflected an association only with 'alogia' (poverty of speech, poverty of content of speech and perseveration) and not with the 'fluent disorganization' component of FTD. Conclusions: This study provides functional imaging support for the view that FTD in schizophrenia may involve impaired executive/frontal function. However, the relationship appears to be exclusively with alogia and not with the variables contributing to fluent disorganization. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC–thalamus network. Methods: We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). Results: We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. Conclusions: We found altered effective and structural connectivity within the ACC–thalamus network in SZ. Our results indicate that ACC–thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling. [ABSTRACT FROM AUTHOR]

Controlling attention during endurance exercises can be a complex task for the human brain. This is mainly because internal bodily cues exert a major influence on one's attentional focus during exercises performed at moderate and high intensities. Further understanding of the cerebral mechanisms that underlie attentional control during endurance tasks has the potential to imbue researchers with greater theoretical knowledge to investigate psychological and psychophysiological responses to exercise. In the present article, the author explores the neural basis of attentional focus during endurance tasks performed at various intensities. Compelling evidence indicates that subcortical regions such as the cingulate gyrus processes interoceptive signals relayed by the thalamus and recreate the sensations of discomfort. Consequently, the right dorsolateral prefrontal cortex may become active in order to partially assuage fatigue-related symptoms. The mechanisms described herein also indicate that frontal and parietal regions function in an orchestrated manner to prioritise processing of task-related information (e.g. distance covered) and prevent irrelevant signals from entering focal awareness during endurance tasks performed at moderate and high intensities. [ABSTRACT FROM AUTHOR]

Objectives Numerous studies show benefits of mid- and late-life activity on neurocognitive health. Yet, few studies have examined how engagement in enriching activities during childhood, when the brain is most plastic, may confer long-term neurocognitive benefits that may be especially important to individuals raised in low-income settings. We examined associations between enriching early-life activities (EELAs) and hippocampal and amygdala volumes in a sample of predominantly African-American, community-dwelling older adults. We further assessed whether these associations were independent of current activity engagement. Methods Ninety participants from the baseline Brain Health Substudy of the Baltimore Experience Corps Trial (mean age: 67.4) completed retrospective activity inventories and an magnetic resonance imaging scan. Volumes were segmented using FreeSurfer. Results Each additional EELA was associated with a 2.3% (66.6 mm3) greater amygdala volume after adjusting for covariates. For men, each additional EELA was associated with a 4.1% (278.9 mm3) greater hippocampal volume. Associations were specific to these regions when compared with the thalamus, used as a control region. Discussion Enriching lifestyle activities during an important window of childhood brain development may be a modifiable factor that impacts lifelong brain reserve, and results highlight the importance of providing access to such activities in historically underserved populations. [ABSTRACT FROM AUTHOR]

Objective: A hallmark of migraine is photophobia. In mice, photophobia‐like behavior is induced by calcitonin gene‐related peptide (CGRP), a neuropeptide known to be a key player in migraine. In this study, we sought to identify sites within the brain from which CGRP could induce photophobia. Design: We focused on the posterior thalamic region, which contains neurons responsive to both light and dural stimulation and has CGRP binding sites. We probed this area with both optogenetic stimulation and acute CGRP injections in wild‐type mice. Since the light/dark assay has historically been used to investigate anxiety‐like responses in animals, we measured anxiety in a light‐independent open field assay and asked if stimulation of a brain region, the periaqueductal gray, that induces anxiety would yield similar results to posterior thalamic stimulation. The hippocampus was used as an anatomical control to ensure that light‐aversive behaviors could not be induced by the stimulation of any brain region. Results: Optogenetic activation of neuronal cell bodies in the posterior thalamic nuclei elicited light aversion in both bright and dim light without an anxiety‐like response in an open field assay. Injection of CGRP into the posterior thalamic region triggered similar light‐aversive behavior without anxiety. In contrast to the posterior thalamic nuclei, optogenetic stimulation of dorsal periaqueductal gray cell bodies caused both light aversion and an anxiety‐like response, while CGRP injection had no effect. In the dorsal hippocampus, neither optical stimulation nor CGRP injection affected light aversion or open field behaviors. Conclusion: Stimulation of posterior thalamic nuclei is able to initiate light‐aversive signals in mice that may be modulated by CGRP to cause photophobia in migraine. [ABSTRACT FROM AUTHOR]

Objectives: Tourette syndrome is a neurodevelopmental disorder commonly associated with involuntary movements, or tics. We currently lack an ideal animal model for Tourette syndrome. In humans, clinical manifestation of tics cannot be captured via functional imaging due to motion artefacts and limited temporal resolution, and electrophysiological studies have been limited to the intraoperative environment. The goal of this study was to identify electrophysiological signals in the centromedian (CM) thalamic nucleus and primary motor (M1) cortex that differentiate tics from voluntary movements.Methods: The data were collected as part of a larger National Institutes of Health-sponsored clinical trial. Four participants (two males, two females) underwent monthly clinical visits for collection of physiology for a total of 6 months. Participants were implanted with bilateral CM thalamic macroelectrodes and M1 subdural electrodes that were connected to two neurostimulators, both with sensing capabilities. MRI scans were performed preoperatively and CT scans postoperatively for localisation of electrodes. Electrophysiological recordings were collected at each visit from both the cortical and subcortical implants.Results: Recordings collected from the CM thalamic nucleus revealed a low-frequency power (3-10 Hz) increase that was time-locked to the onset of involuntary tics but was not present during voluntary movements. Cortical recordings revealed beta power decrease in M1 that was present during tics and voluntary movements.Conclusion: We conclude that a human physiological signal was detected from the CM thalamus that differentiated tic from voluntary movement, and this physiological feature could potentially guide the development of neuromodulation therapies for Tourette syndrome that could use a closed-loop-based approach. [ABSTRACT FROM AUTHOR]

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Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels. [ABSTRACT FROM AUTHOR]

Introduction: Executive dysfunction is common in dementia with Lewy bodies (DLB). The pulvinar nucleus plays a role in executive control and synchronizes with cortical regions in the salience network that are vulnerable to Lewy pathology. Objective: We investigated the pulvinar subregions in patients with mild DLB and their associations with executive function. Methods: The sample consisted of 38 DLB patients and 38 age- and sex-matched normal controls. We evaluated cognitive function using the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. We obtained four pulvinar nuclei using preprocessed T1-weighted magnetic resonance images. We compared volumes and textures of the DLB patients and the normal controls for each nucleus. We used a linear regression to determine the association of textures and neuropsychological test scores. Results: The DLB patients showed comparable volumes to the normal controls in all pulvinar nuclei. However, the DLB patients showed different texture of the left medial pulvinar (PuM) from the normal controls. The entropy, contrast, and cluster shade were lower but autocorrelation of left PuM was higher in the DLB patients compared to the normal controls. These texture features of the left PuM were associated with the set-shifting performance measured by the Trail Making Test. Conclusions: In DLB, the left PuM may be altered from early stage, which may contribute to the development of executive dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: A growing body of research has emerged on the resting state and the default mode of the brain. Functional connectivity studies, which lately dominate this research area, have confirmed that regions such as the cortical mid-line structures, as well as parietal-temporal regions are tightly interconnected within the default mode network (DMN). However, little is known about the activity patterns of resting state related brain regions detected in fMRI studies using the generalized linear model (GLM) in a whole brain analysis. The aim of the current study was to investigate the activity changes among brain regions identified through GLM during the transition from task to rest and the prolongation of rest. Methods: A picture imagination task, as a controlled thought content task, was used in order to minimize confounding factors such as a visual stimulus or a motor response. Results: The present study revealed a consistent fluctuating activation pattern of the dorsal anterior cingulate cortex (dACC), the posterior cingulate cortex (PCC), thalamus, primer motor area (PMA), insula, brain stem and bilateral putamen during the transition from task to the early phase of the resting state and the prolongation of the resting state. All regions showed increased activation during the detachment from task. However, this increased activation was not sustained during the extension of rest, replaced with a decreased activation at the late phase of rest. The increased activation of resting state regions might help with the detachment from the current task. Among these regions dACC, insula and putamen were correlated in all conditions. Conclusion: These findings underline the importance of the activation increase of the cortical mid-line regions and insula in the transition from task to the resting state. [ABSTRACT FROM AUTHOR]

Introduction. The aim of this meta-analysis was to evaluate the effects of STN DBS on sleep quality and restless leg symptoms in individuals with PD. Methods. We searched the PubMed, Web of Science, EMBASE, CNKI, and WANFANG databases published between 1990 and 2019. The articles included were those that contained both pre- and postsurgery data acquired using International RLS Study Group criteria and the Pittsburgh sleep quality index (PSQI) questionnaire with patients' follow-up of at least three months. All studies that met the quality requirements were included in a meta-analysis performed using STATA 12.0 software. Results. Of 73 articles identified, 7 studies comprising 82 patients were qualified for the current meta-analysis. After adjusting for heterogeneity in study effect sizes, the random effects meta-analysis indicated that STN DBS improved sleep quality and restless leg symptoms significantly (SMD = −1.111, 95% CI: −1.918∼−0.304, P=0.007). Subgroup analysis showed that different sleep scoring criteria had different effects on the condition of sleeping after surgery. Conclusions. STN DBS is a powerful method in the management of sleep quality and restless leg symptoms in PD patients, but its long-term effects with larger populations must be thoroughly assessed. [ABSTRACT FROM AUTHOR]

Studies on Parkinson's disease (PD) are becoming very popular on multidisciplinary platforms. The development of predictable telemonitored early detection models has become closely related to many different research areas. The aim of this article is to develop a visual performance test that can examine the effects of Parkinson's disease on the visual cortex, which can be a subtitle scoring test in UPDRS. However, instead of showing random images and asking for discrepancies between them, it is expected that the questions to be asked to patients should be provable in the existing cortex models, should be deduced between the images, and produce a reference threshold value to compare with the practical results. In a developed test, horizontal and vertical motion blur orientation was applied to natural image samples, and then neural outputs were produced by representing three (original-horizontal-vertical) image groups with the Layer 4 (L4) cortex model. This image representation is then compared with a filtering model which is very similar to thalamus' functionality. Thus, the linear problem-solving performance of the L4 cortex model is also addressed in the study. According to the obtained classification results, the L4 model produces high-performance success rates compared to the thalamic model, which shows the adaptation power of the visual cortex on the image pattern differences. In future studies, developed motion-based visual tests are planned to be applied to PD patient groups/controls, and their performances with mathematical threshold values will be examined. [ABSTRACT FROM AUTHOR]

Obsessive--compulsive disorder (OCD) affects 1%-3% of children worldwide and has a profound impact on quality of life for patients and families. Although our understanding of the underlying etiology remains limited, data from neuroimaging and genetic studies as well as the efficacy of serotonergic medications suggest the disorder is associated with the fundamental alterations in the function of cortico-striato-thalamocortical circuits. Significant delays to diagnosis are common, ultimately leading to more severe functional impairment with long-term developmental consequences. The clinical assessment requires a detailed history of specific OCD symptoms as well as psychiatric and medical comorbidities. Standardized assessment tools may aid in evaluating and tracking symptom severity and both individual and family functioning. In the majority of children, an interdisciplinary approach that combines cognitive behavioral therapy with a serotonin reuptake inhibitor leads to meaningful symptom improvement, although some patients experience a chronic, episodic course. There are limited data to guide the management of treatment-refractory illness in children, although atypical antipsychotics and glutamate-modulating agents may be used cautiously as augmenting agents. This review outlines a clinical approach to the diagnosis and management of OCD, highlighting associated challenges, and limitations to our current knowledge. [ABSTRACT FROM AUTHOR]

Background: Neuromodulation of the cerebello-thalamo-cortical (CTC) circuit via thalamic stimulation is an effective therapy for essential tremor (ET). In order to develop non-invasive neuromodulation approaches, clinically relevant thalamo-cortical connections must be elucidated. Methods: Twenty-eight subjects (18 ET patients and 10 controls) underwent MRI diffusional kurtosis imaging (DKI). A deterministic fiber-tracking algorithm based on DKI was used, with a seeding region placed at the ventral intermediate nucleus (Vim--located based on intraoperative physiology) to the ending regions at the supplementary motor area (SMA), pre-SMA, or primary motor cortex. One-tailed t-tests were performed to compare groups, and associations with tremor severity were determined by Pearson correlations. All p-values were adjusted for multiple comparisons using Bonferroni correction. Results: There was a decrease in the mean diffusivity (MD) in patients compared to controls in all three tracts: Vim-M1 (ET 0.87, control 0.96, p < 0.01), Vim-SMA (ET 0.86, control 0.96, p < 0.05), and Vim-pre-SMA (ET 0.87, control 0.95, p < 0.05). There was a significant positive correlation between Tremor Rating Scale score and MK (r = 0.471, p = 0.033) and mean FA (r = 0.438, p = 0.045) for the Vim-SMA tract, and no significant correlation for the Vim-pre-SMA or Vim-M1 tracts was found. Discussion: Patients with ET demonstrated a reinforcement of Vim-cortical connectivity, with higher Vim-SMA connectivity being associated with greater tremor severity. This finding suggests that the Vim-SMA connection is relevant to the underlying pathophysiology of ET, and inhibition of the SMA may be an effective therapeutic approach. [ABSTRACT FROM AUTHOR]

The thalamus is believed to play crucial role in processing viscero-sensory information, and regulating the activity of amygdala in patients with panic disorder (PD). Previous functional neuroimaging studies have detected abnormal activation in the thalamus in patients with PD compared with healthy control subjects (HC). Very few studies, however, have investigated for volumetric abnormalities in the thalamus in patients with PD. Furthermore, to the best of our knowledge, no previous study has investigated for shape abnormalities in the thalamus in patients with PD. Twenty-five patients with PD and 25 HC participants (all female) were recruited for the study. A voxel-wise volume comparison analysis and a vertex-wise shape analysis were conducted to evaluate structural abnormalities in the PD patients compared to HC. The patients with PD demonstrated significant gray matter volume reductions in the thalamus bilaterally, relative to the HC. The shape analysis detected significant inward deformation in some thalamic regions in the PD patients, including the anterior nucleus, mediodorsal nucleus, and pulvinar nucleus. PD patients showed shape deformations in key thalamic regions that are believed to play a role in regulating emotional and cognitive functions. [ABSTRACT FROM AUTHOR]

TBI and PTSD are global issues and are often referred to as signature wounds of the Iraq and Afghanistan wars. Art therapy can provide unique insights into military service members’ injuries and states of mind via externalisation within an art product; however, interpretation of results is complex and subjective. Advance neuroimaging tools such as resting state fMRI can be employed to demonstrate objective measures of brain structure and activity. This case series highlights two distinct patient profiles, suggesting a relationship between resting state connectivity maps and dynamic thalamic connectivity (as well as PCL-C and NSI scores and brain scars) and the corresponding visual elements of masks made during art therapy treatment. Ultimately, this study indicates a need for future research examining potential neurological changes pre- and post-art therapy treatment. [ABSTRACT FROM AUTHOR]

Similarities in neural activation patterns in obese and substance‐dependent subjects led to the food addiction concept, but studies exploiting this issue for obesity stratification are missing. We assessed brain activation in response to food cues using 18F‐2‐fluoro‐2‐deoxy‐glucose‐PET in 36 overweight women, stratified by low or high food addiction groups according to the Yale Food Addiction Scale (YFAS). Assessments were repeated after a 3‐month diet. We found greater activation in thalamus, hypothalamus, midbrain, putamen, and occipital cortex (reward), but not in prefrontal and orbitofrontal cortices (control/reward receipt) in the high‐YFAS versus low‐YFAS group. In high‐YFAS subjects, orbitofrontal responsiveness was inversely related to YFAS severity and hunger rating, and positive associations were observed between regional brain activation and lipid intake. A 3‐month diet abolished group differences in brain activation. Our data suggest that food addiction distinguishes an overweight phenotype that can be reversed by diet, opening to personalized strategies in obesity treatment. [ABSTRACT FROM AUTHOR]

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy. [ABSTRACT FROM AUTHOR]

Dopamine exerts modulatory signals on cortex-basal ganglia circuits to enable flexible motor control. Parkinson's disease is characterized by a loss of dopaminergic innervation in the basal ganglia leading to complex motor and non-motor symptoms. Clinical symptom alleviation through dopaminergic medication and deep brain stimulation in the subthalamic nucleus likely depends on a complex interplay between converging basal ganglia pathways. As a unique translational research platform, deep brain stimulation allows instantaneous investigation of functional effects of subthalamic neuromodulation in human patients with Parkinson's disease. The present study aims at disentangling the role of the inhibitory basal ganglia pathways in cognitive and kinematic aspects of automatic and controlled movements in healthy and parkinsonian states by combining behavioural experiments, clinical observations, whole-brain deep brain stimulation fibre connectivity mapping and computational modelling. Twenty patients with Parkinson's disease undergoing subthalamic deep brain stimulation and 20 age-matched healthy controls participated in a visuomotor tracking task requiring normal (automatic) and inverted (controlled) reach movements. Parkinsonian patients on and off deep brain stimulation presented complex patterns of reaction time and kinematic changes, when compared to healthy controls. Stimulation of cortico-subthalamic fibres was correlated with reduced reaction time adaptation to task demand, but not kinematic aspects of motor control or alleviation of Parkinson's disease motor signs. By using clinically, behaviourally and fibre tracking informed computational models, our study reveals that loss of cognitive adaptation can be attributed to modulation of the hyperdirect pathway, while kinematic depends on suppression of indirect pathway activity. Our findings suggest that hyperdirect and indirect pathways, converging in the subthalamic nucleus, are differentially involved in cognitive aspects of cautious motor preparation and kinematic gain control during motor performance. Subthalamic deep brain stimulation modulates but does not restore these functions. Intelligent stimulation algorithms could re-enable flexible motor control in Parkinson's disease when adapted to instantaneous environmental demand. Our results may inspire new innovative pathway-specific approaches to reduce side effects and increase therapeutic efficacy of neuromodulation in patients with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Deep brain stimulation enables the delivery of therapeutic interventions to otherwise inaccessible areas of the brain while, at the same time, offering the unique opportunity to record from these same regions in awake patients. The posterior ventrolateral thalamus has become a reliable deep brain stimulation target for medically-refractory patients suffering from essential tremor. However, the contribution of the thalamus in essential tremor, and even whether posterior ventrolateral thalamus is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the posterior ventrolateral thalamus that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during deep brain stimulation surgery. Data were obtained from 10 severely affected patients with essential tremor (12 hemispheres) undergoing deep brain stimulation surgery. Our results demonstrate power and coherence maxima located in the inferior posterior ventrolateral thalamus and immediate ventral region. Moreover, we identified distinct yet overlapping clusters of predominantly efferent (driving) and afferent (feedback) activity, with a preference for more efferent contributors, consistent with a net role in the driving of tremor output. Finally, we demonstrate that resolvable thalamic spiking activity directly relates to background activity and that the strength of tremor may be dictated by phase relationships between efferent and afferent pockets in the posterior ventrolateral thalamus. Taken together, these results provide important evidence for the role of the inferior posterior ventrolateral thalamus and its border region in essential tremor pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high resolution segregated deep brain stimulation electrodes. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi‐substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes. Design: Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors). Setting: Two large population‐based twin samples from the United States and Australia. Participants: A total of 622 young Australian adults [66% female; μage = 25.9, standard deviation SD) = 3.6] and 474 middle‐aged US males (μage = 56.1SD = 2.6) of predominately Anglo‐Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded. Measurements: Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life‐time multi‐substance use, maximum cannabis use in the young adults and regular cannabis use in the middle‐aged males. Findings: After correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle‐aged males. Conclusions: In exploratory analyses based on young adult and middle‐aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume. [ABSTRACT FROM AUTHOR]

Impairment of naming function is a critical problem for temporal lobe epilepsy patients, yet the neural correlates of the disruption of temporal lobe language networks are poorly understood. Using functional MRI, we investigated the activation and task-related functional connectivity of left temporal lobe language networks and their relation to clinical naming performance and disease characteristics. We studied 59 adult patients with temporal lobe epilepsy (35 left temporal lobe epilepsy) and 32 healthy controls with auditory and visual naming functional MRI tasks. Time series of activation maxima in the left posterior inferior temporal lobe were extracted to create a psychophysiological interaction regressor for subsequent seed-based whole-brain task-related functional connectivity analyses. Correlational analyses were performed to assess the association of functional MRI activation and functional connectivity with clinical naming scores, age of onset of epilepsy, and duration of epilepsy. Auditory naming elicited activation in the left posterior inferior temporal gyrus and visual naming in the left fusiform gyrus across all groups. Activations in the left inferior temporal gyrus, left thalamus and left supplementary motor region during auditory naming as well as left fusiform activations during picture naming correlated with better clinical naming performance. Functional connectivity analyses indicated coupling of left posterior inferior temporal regions to bilateral anterior and posterior temporal lobe regions and the bilateral inferior precentral gyrus as well as contralateral occipital cortex. Stronger functional connectivity was associated with better clinical naming performance in all groups. In patients with left temporal lobe epilepsy only, functional connectivity increased with later age of onset of epilepsy and shorter disease duration. This suggests that onset of seizures early in life and prolonged disease duration lead to disrupted recruitment of temporal lobe networks ipsilateral to the seizure focus, which might account for naming deficits in temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to describe a robust method with high time resolution for estimating the cortico-thalamo-cortical (CTC) loop strength and the delay when using a scalp electroencephalography (EEG) and to illustrate its applicability for analyzing the wake-sleep transition.Methods: The basic framework for the proposed method is the parallel use of a physiological model and a parametric phenomenological model: a neural field theory (NFT) of the corticothalamic system and an autoregressive (AR) model. The AR model is a "stochastic" model that shortens the time taken to extract spectral features and is also a "linear" model that is free from the local-minimum problem. From the relationship between the transfer function of the AR model and the transfer function of the NFT in the low frequency limit, we successfully derived a direct expression of CTC loop strength and the loop delay using AR coefficients.Results: Using this method to analyze sleep-EEG data, we were able to clearly track the wake-to-sleep transition, as the estimated CTC loop strength (c2) decreased to almost zero. We also found that the c2-distribution during nocturnal sleep is clearly bimodal in nature, which can be well approximated by the superposition of two Gaussian distributions that correspond to sleep and wake states, respectively. The estimated loop delay distributed ∼0.08 s, which agrees well with the previously reported value estimated by other methods, confirming the validity of our method.Conclusions: A robust method with high time resolution was developed for estimating the cortico-thalamo-cortical loop strength and the delay when using a scalp electroencephalography. This method can contribute not only to detecting the wake-sleep transition, but also to further understanding of the transition, where the cortico-thalamo-cortical loop is thought to play an important role. [ABSTRACT FROM AUTHOR]

Objective: In this pilot study, the purpose is to investigate if a series of sphenopalatine ganglion (SPG) blockade treatments modulate the functional connectivity within the salience and central executive network (CEN) in chronic migraine with medication overuse headaches (CMw/MOH). Background: Using intranasal local anesthesia to block the SPG for the treatment of various headache disorders has been employed in clinical practice since the early 1900s. However, the exact mechanism of how SPG modulate resting state intrinsic functional brain networks connectivity remains to be elucidated. This pilot study seeks to understand the resting state connectivity changes in salience and CENs, with emphasis on the mesocorticolimbic systems, before and after a series of SPG block treatments. Methods: Using fMRI, resting state connectivity was derived from predefined networks of nodes (regions of interests) for the salience (27 nodes, 351 connections) and CENs (17 nodes, 136 connections). After treatments, a paired samples t‐test (with 10,000 permutations to correct for multiple comparison) was used to evaluate changes in the intranetwork resting state functional connectivity within the salience and executive networks, as well as the overall network connectivity strength. Results: When comparing connectivity strength at baseline to that at the end of treatment in our cohort of 10 CMw/MOH participants, there were several connections within the salience (n = 9) and executive (n = 8) networks that were significantly improved. Within the salience network, improved connectivity was observed between the prefrontal cortex and various regions of the insula, basal ganglia, motor, and frontal cortex. Additionally, changes in connectivity were observed between regions of the temporal cortex with the basal ganglia and supramarginal gyrus. Within the CEN, improved connectivity was observed between the prefrontal cortex and regions of the anterior thalamus, caudate, and frontal cortex. After treatment, the overall CEN connectivity was significantly improved (Baseline 0.00 ± 0.08; 6 weeks 0.03 ± 0.09, P = .01); however, the overall salience network connectivity was not significantly improved (Baseline −0.01 ± 0.10; 6 weeks 0.01 ± 0.12, P = .26). Additionally, after treatment, there was a significant reduction in the number of moderate/severe headache days per month (Baseline 21.1 ± 6.6; 6 weeks 11.2 ± 6.5, P < .001), HIT‐6 (Baseline 66.1 ± 2.6; 6 weeks 60.2 ± 3.6, P < .001), and PHQ‐9 (Baseline 12.4 ± 5.7; 6 weeks 6.1 ± 3.6, P = .008) scores. Conclusion: In this longitudinal fMRI study, we observed improved functional connectivity within both networks, primarily involving connectivity between regions of the prefrontal cortex and limbic (cortical‐limbic) structures, and between different cortical (cortical‐cortical) regions after a series of repetitive SPG blockades. The overall CEN strength was also improved. Our results suggest that recurrent parasympathetic inhibition via SPG is associated with improved functional connectivity in brain regions critical to pain processing in CMw/MOH. [ABSTRACT FROM AUTHOR]

Corpus callosum agenesis (CCA) is a clinical condition accompanied by various aneuploidy and genetic syndromes. We identified the development of the corpus callosum (CC) in 278 patients before 18 weeks of gestational age by visualising the pericallosal artery (PCA) in the callosal sulcus and changes in the lengths and ratios of the midbrain (MB) and falx (F), which suggested elevation of the third ventricle and thalamus due to CCA in the first trimester. We succeeded in visualising the path of the PCA in 273 patients. As expected, we observed an increase in the lengths of the MB and F throughout the pregnancies. The MB:F ratio was 0.5-0.6, and it was independent of gestational age. In all 278 patients, the MB:F ratio was <0.6 (95th percentile = 0.79). We observed the presence of the CC during anatomical screening at gestational weeks 18-24. Visualisation of the PCA path (98% sensitivity) and calculation of the MB:F ratio <95th percentile (0.79-100% sensitivity) had very high sensitivity that indirectly confirmed the presence of the CC in the first trimester of pregnancy. Impact statement What is already known on this subject: After reading the articles for detecting the absence of corpus callosum (CC) at first trimester with midbrain (MB) and falx (F) measurement by Lachmann et al. ( 2013 ) and visualising pericallosal artery (PCA) as an indirect sign of CC agenesis by Pati et al. ( 2012 ), we aimed to have a look for our records visualising PCA in callosal sulcus and measure MB-F, as well as their ratios for an indirect sign of 'presence' of CC at first trimester. What the results of this study add: In recent literature, it is not possible to find many articles suggesting the presence of CC between 11 and 13 weeks of gestation. Díaz-Guerrero et al. ( 2013 ) and Pati et al. ( 2012 ) has researched visualising PCA path. Lachmann et al. ( 2013 ) reported an article for MB and F measurements in early suspicion of CC agenesis. Our study will be the first article in visualising PCA path and measuring MB-F lengths as well as their ratios for 'presence' of CC with high sensitivity rates (98% and 100%). What are the implications of these findings for clinical practice and/or further research: This study encourages clinicians visualising PCA path and measure MB-F lengths when they will try to visualise repetitive times and see how it is an easy procedure when you get used to it. [ABSTRACT FROM AUTHOR]

Massive corticothalamic afferents originating from layer 6a of primary sensory cortical areas modulate sensory responsiveness of thalamocortical neurons and are pivotal for shifting neuronal firing between burst and tonic modes. The influence of the corticothalamic pathways on the firing mode and sensory gain of thalamic neurons has only been extensively examined in anesthetized animals, but has yet to be established in the awake state. We made lesions of the rat barrel cortex and on the following day recorded responses of single thalamocortical and thalamic reticular neurons to a single vibrissal deflection in the somatosensory system during wakefulness. Our results showed that the cortical lesions shifted the response of thalamic neurons towards bursting, elevated the response probability and the gain of thalamocortical neurons, predominantly of recurring responses. In addition, after the lesions, the spontaneous activities of the vibrissa-responsive thalamic neurons, but not those of vibrissa-unresponsive cells, were typified by waxing-and-waning spindle-like rhythmic spiking with frequent bursting. In awake rats with intact cortex, identified layer 6a corticothalamic neurons responded to a single vibrissal deflection with short latencies that matched those of layer 4 neurons, strongly suggesting the existence of an immediate corticothalamic feedback. The present results show the importance of corticothalamic neurons in shaping thalamic activities during wakefulness. [ABSTRACT FROM AUTHOR]

Background: Many cross-sectional voxel-based morphometry (VBM) investigations have shown significant inverse correlations between chronological age and gray matter (GM) volume in several brain regions in healthy humans. However, few VBM studies have documented GM decrements in the healthy elderly with repeated MRI measurements obtained in the same subjects. Also, the extent to which the APOE ɛ4 allele influences longitudinal findings of GM reduction in the healthy elderly is unclear.Objective: Verify whether regional GM changes are associated with significant decrements in cognitive performance taking in account the presence of the APOE ɛ4 allele.Methods: Using structural MRI datasets acquired in 55 cognitively intact elderly subjects at two time-points separated by approximately three years, we searched for voxels showing significant GM reductions taking into account differences in APOE genotype.Results: We found global GM reductions as well as regional GM decrements in the right thalamus and left parahippocampal gyrus (p < 0.05, family-wise error corrected for multiple comparisons over the whole brain). These findings were not affected by APOE ɛ4.Conclusions: Irrespective of APOE ɛ4, longitudinal VBM analyses show that the hippocampal region and thalamus are critical sites where GM shrinkage is greater than the degree of global volume reduction in healthy elderly subjects. [ABSTRACT FROM AUTHOR]

Neurosurgical interventions have been used to treat PD for over a century. We examined the changing landscape of surgery for PD to appraise the value of various procedures in the context of advances in our understanding and technology. We assessed the number of articles published on neurosurgical procedures for PD over time as an albeit imprecise surrogate for their usage level. We identified over 8,000 publications associated with PD surgery. Over half the publications were on DBS. The field of DBS for PD showed a rapid rise in articles, but is now in a steady state. Thalamotomy and, to a lesser extent, pallidotomy follow a biphasic publication distribution with peaks approximately 30 years apart. Articles on gene therapy and transplantation experienced initial rapid rises and significant recent declines. Procedures using novel technologies, including gamma knife and focused ultrasound, are emerging, but are yet to have significant impact as measured by publication numbers. Pallidotomy and thalamotomy are prominent examples of procedures that were popular, declined, and re-emerged and redeclined. Transplantation and gene therapy have never broken into clinical practice. DBS overtook all procedures as the dominant surgical intervention and drove widespread use of surgery for PD. Notwithstanding, the number of DBS articles appears to have plateaued. As advances continue, emerging treatments may compete with DBS in the future. © 2017 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Invasive pituitary adenomas can infiltrate the dura mater, sphenoid sinus, or cranial bone. Endoscopic transsphenoidal sinus surgery is considered the standard of care; however, several potential complications must be noted. These complications can include cerebrospinal fluid leaks, infection, bleeding, optic nerve damage, and endocrinological complications such as diabetes insipidus. We present a case of a 69-year-old female with multiple recurrent invasive pituitary adenomas who has previously undergone 5 transsphenoidal procedures. Intraoperatively, the patient suffered from a left-sided carotid artery injury that was repaired with a muscle graft. Management of carotid artery injury during transsphenoidal surgery is optimized in a step-by-step approach which includes early recognition of the injury, briefing the surgical team, immediate control using compression, use of additional tissue graft for wound repair, and postoperative care. Through the use of the approach mentioned above, we were able to control the complication successfully. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) infects the face and can result in chronic, debilitating pain. The mechanism for this pain is unknown and current treatment is often not effective, thus investigations into the pain pathway become vital. Pain itself is multidimensional, consisting of sensory and affective experiences. One of the primary brain substrates for transmitting sensory signals in the face is the ventral posterior medial/posterior lateral thalamus (VPM/VPL). In addition, the anterior cingulate cortex (ACC) has been shown to be vital in the affective experience of pain, so investigating both of these areas in freely behaving animals was completed to address the role of the brain in VZV-induced pain. Our lab has developed a place escape avoidance paradigm (PEAP) to measure VZV-induced affective pain in the orofacial region of the rat. Using this assay as a measure of the affective pain experience a significant response was observed after VZV injection into the whisker pad and after VZV infusion into the trigeminal ganglion. Local field potentials (LFPs) are the summed electrical current from a group of neurons. LFP in both the VPM/VPL and ACC was attenuated in VZV injected rats after inhibition of neuronal activity. This inhibition of VPM/VPL neurons was accomplished using a designer receptor exclusively activated by a designer drug (DREADD). Immunostaining showed that cells within the VPM/VPL expressed thalamic glutamatergic vesicle transporter-2, NeuN and DREADD suggesting inhibition occurred primarily in excitable neurons. From these results we conclude: (1) that VZV associated pain does not involve a mechanism exclusive to the peripheral nerve terminals, and (2) can be controlled, in part, by excitatory neurons within the VPM/VPL that potentially modulate the affective experience by altering activity in the ACC. [ABSTRACT FROM AUTHOR]

This review updates the findings about the anatomical distribution (using immunohistochemical techniques) and possible functions of D-glutamate in the central nervous system of mammals, as well as compares the distribution of D-glutamate with the distribution of the most studied D-amino acids: D-serine and D-aspartate. The protocol used to obtain highly specific antisera directed against D-amino acids is also reported. Immunoreactivity for D-glutamate was found in dendrites and cell bodies, but not in nerve fibers. Perikarya containing D-glutamate were found in the mesencephalon and thalamus. The highest density of cell bodies was found in the dorsal raphe nucleus, the mesencephalic central grey matter, the superior colliculus, and in the subparafascicular thalamic nucleus. In comparison with the distribution of immunoreactive cell bodies containing D-serine or D-aspartate, the distribution of D-glutamate-immunoreactive perikarya is less widespread. Currently, the physiological actions mediated by D-glutamate in the brain are unknown but the restricted neuroanatomical distribution of this D-amino acid suggests that D-glutamate could be involved in very specific physiological mechanisms. In this sense, the possible functional roles of D-glutamate are discussed. [ABSTRACT FROM AUTHOR]

Background: Ketamine is a frequently used intravenous anesthetic, which can reversibly induce loss of consciousness (LOC). Previous studies have demonstrated that thalamocortical system is critical for information transmission and integration in the brain. The ventral posteromedial nucleus (VPM) is a critical component of thalamocortical system. Glutamate is an important excitatory neurotransmitter in the brain and may be involved in ketamine-induced LOC. Methods: The study used whole-cell patch-clamp to observe the effect of ketamine (30 µM-1000 µM) on glutamatergic neurotransmission in VPM slices. Results: Ketamine significantly decreased the amplitude of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs), but only higher concentration of ketamine (300 µM and 1000 µM) suppressed the frequency of sEPSCs. Ketamine (100 µM-1000 µM) also decreased the amplitude of glutamatergic miniature excitatory postsynaptic currents (mEPSCs), without altering the frequency. Conclusions: In VPM neurons, ketamine attenuates the glutamatergic neurotransmission mainly through postsynaptic mechanism and action potential may be involved in the process. [ABSTRACT FROM AUTHOR]

Background: We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor.Methods: Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (≥48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications.Results: There was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long-term follow-up (8 of 17). The latency of symptoms on standing significantly improved, both in the short-term (P = 0.001) and in the long-term (P = 0.018). Three patients obtained no/minimal benefit from the procedure.Conclusions: Deep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Neurons in cortical layer 5B (L5B) connect the cortex to numerous subcortical areas. Possibly the best-studied L5B cortico–subcortical connection is that between L5B neurons in the rodent barrel cortex (BC) and the posterior medial nucleus of the thalamus (POm). However, the spatial organization of L5B giant boutons in the POm and other subcortical targets is not known, and therefore it is unclear if this descending pathway retains somatotopy, i.e., body map organization, a hallmark of the ascending somatosensory pathway. We investigated the organization of the descending L5B pathway from the BC by dual-color anterograde labeling. We reconstructed and quantified the bouton clouds originating from adjacent L5B columns in the BC in three dimensions. L5B cells target six nuclei in the anterior midbrain and thalamus, including the posterior thalamus, the zona incerta, and the anterior pretectum. The L5B subcortical innervation is target specific in terms of bouton numbers, density, and projection volume. Common to all target nuclei investigated here is the maintenance of projection topology from different barrel columns in the BC, albeit with target-specific precision. We estimated low cortico–subcortical convergence and divergence, demonstrating that the L5B corticothalamic pathway is sparse and highly parallelized. Finally, the spatial organization of boutons and whisker map organization revealed the subdivision of the posterior group of the thalamus into four subnuclei (anterior, lateral, medial, and posterior). In conclusion, corticofugal L5B neurons establish a widespread cortico–subcortical network via sparse and somatotopically organized parallel pathways. [ABSTRACT FROM AUTHOR]