Mindfulness and Attention Deficit Hyperactivity Disorder: A Neuropsychological Perspective.

ABSTRACT: Understanding the underlying mechanisms of mindfulness has been a hot topic in recent years, not only in clinical fields but also in neuroscience. Most neuroimaging findings demonstrate that critical brain regions involved in mindfulness are responsible for cognitive functions and mental states. However, the brain is a complex system operating via multiple circuits and networks, rather than isolated brain regions solely responsible for specific functions. Mindfulness-based treatments for attention deficit hyperactivity disorder (ADHD) have emerged as promising adjunctive or alternative intervention approaches. We focus on four key brain circuits associated with mindfulness practices and effects on symptoms of ADHD and its cognitive dysfunction, including executive attention circuit, sustained attention circuit, impulsivity circuit, and hyperactivity circuit. We also expand our discussion to identify three key brain networks associated with mindfulness practices, including central executive network, default mode network, and salience network. We conclude by suggesting that more research efforts need to be devoted into identifying putative neuropsychological mechanisms of mindfulness on how it alleviates ADHD symptoms.

Characterization of brain functional connectivity in treatment-resistant depression.

OBJECTIVE: To characterize the functional connectivity (FC) of target brain regions for deep brain stimulation (DBS) in patients with treatment-resistant depression (TRD), and to evaluate its gender and brain lateralization dependence. METHODS: Thirty-one TRD patients and twenty-nine healthy control (HC) subjects participated. FC of subcallosal cingulate gyrus (SCG), ventral caudate (VCa), nucleus accumbens (NAc), lateral habenula (LHb), and inferior thalamic peduncle (ITP) were evaluated using resting-state fMRI. FC was characterized by calculating the nodal 'degree', a major feature of the graph theory. RESULTS: The degree measures of the left and right VCa, the left LHb, and the left ITP were significantly greater in the TRD than in the HC group. The degree was greater in females with TRD in all these regions except the right LHb. Finally, the left hemisphere was generally more affected by depression and presented significant degrees in LHb and ITP regions of the patients. CONCLUSION: Our findings demonstrate the ability of degree to characterize brain FC and identify the regions with abnormal activities in TRD patients. This implies that the degree may have the potential to be used as an important graph-theoretical feature to further investigate the mechanisms underlying TRD, and consequently along with other diagnostic markers, to assist in the determination of the appropriate target region for DBS treatment in TRD patients.

Ictal and interictal brain activation in episodic migraine: Neural basis for extent of allodynia.

In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)-to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as "switched off" in generalized allodynia.

Mind-body (hypnotherapy) treatment of women with urgency urinary incontinence: changes in brain attentional networks.

BACKGROUND: Prior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment. OBJECTIVE: This study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging. STUDY DESIGN: A subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks. RESULTS: After treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001). CONCLUSION: Successful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury.

Cortical disinhibition is the underlying pathological alteration contributing to neuropathic pain associated with peripheral nerve injury. Nerve injury resulting in disinhibition of the anterior cingulate cortex has been reported. However, the effect of optogenetic inhibition of the anterior cingulate cortex (ACC) on the sensory component of nerve injury-induced neuropathic pain has not been well studied. To investigate the feasibility of optogenetic ACC modulation, we injected an optogenetic virus or a null virus into the ACC of a nerve injury-induced neuropathic pain model. The unilateral ACC was modulated, and the optogenetic effect was measured by mechanical and thermal sensitivity tests. The assessment was performed in "pre-light off," "stimulation-yellow light on," and "post-light off" states. Optogenetic inhibition of the ACC in injury models revealed improved mechanical and thermal latencies with profound pain-relieving effects against nerve injury-induced neuropathic pain. The sensory thalamic discharge in electrophysiological in vivo recordings was also altered during laser stimulation. This finding indicates that hyperactivity of the ACC in nerve injury increases output to the spinothalamic tract through direct or indirect pathways. The direct photoinhibition of ACC neurons could play a vital role in restoring equilibrium and provide novel insight into techniques that can assuage peripheral nerve injury-induced neuropathic pain.

Preterm birth leads to impaired rich-club organization and fronto-paralimbic/limbic structural connectivity in newborns.

Prematurity disrupts brain development during a critical period of brain growth and organization and is known to be associated with an increased risk of neurodevelopmental impairments. Investigating whole-brain structural connectivity alterations accompanying preterm birth may provide a better comprehension of the neurobiological mechanisms related to the later neurocognitive deficits observed in this population. Using a connectome approach, we aimed to study the impact of prematurity on neonatal whole-brain structural network organization at term-equivalent age. In this cohort study, twenty-four very preterm infants at term-equivalent age (VPT-TEA) and fourteen full-term (FT) newborns underwent a brain MRI exam at term age, comprising T2-weighted imaging and diffusion MRI, used to reconstruct brain connectomes by applying probabilistic constrained spherical deconvolution whole-brain tractography. The topological properties of brain networks were quantified through a graph-theoretical approach. Furthermore, edge-wise connectivity strength was compared between groups. Overall, VPT-TEA infants' brain networks evidenced increased segregation and decreased integration capacity, revealed by an increased clustering coefficient, increased modularity, increased characteristic path length, decreased global efficiency and diminished rich-club coefficient. Furthermore, in comparison to FT, VPT-TEA infants had decreased connectivity strength in various cortico-cortical, cortico-subcortical and intra-subcortical networks, the majority of them being intra-hemispheric fronto-paralimbic and fronto-limbic. Inter-hemispheric connectivity was also decreased in VPT-TEA infants, namely through connections linking to the left precuneus or left dorsal cingulate gyrus - two regions that were found to be hubs in FT but not in VPT-TEA infants. Moreover, posterior regions from Default-Mode-Network (DMN), namely precuneus and posterior cingulate gyrus, had decreased structural connectivity in VPT-TEA group. Our finding that VPT-TEA infants' brain networks displayed increased modularity, weakened rich-club connectivity and diminished global efficiency compared to FT infants suggests a delayed transition from a local architecture, focused on short-range connections, to a more distributed architecture with efficient long-range connections in those infants. The disruption of connectivity in fronto-paralimbic/limbic and posterior DMN regions might underlie the behavioral and social cognition difficulties previously reported in the preterm population.

Regulated aberrant amygdala functional connectivity in premenstrual syndrome via electro-acupuncture stimulation at sanyinjiao acupoint（SP6）.

Background: Acupuncture is an effective therapy for premenstrual syndrome (PMS). However, the mechanisms behind this method are still unclear. Our previous study found that aberrant amygdala resting-state functional networks were involved in PMS. Thereby, a deep investigation on the alterations of amygdala resting-state functional networks induced by acupuncture stimulation might contribute to a better understanding of the intricate mechanisms of acupuncture treatment on PMS. Methods: Twenty three PMS patients were recruited in this study. All patients received a 6-minute electro-acupuncture stimulation (EAS) at Sanyinjiao acupoint (SP6) and underwent two 6-minute resting-state fMRI scannings before and after EAS. With amygdala as the seed region, functional connectivity (FC) method was adopted to examine EAS-related modulation of intrinsic connectivity in PMS patients by comparing pre-EAS. Results: The results showed that EAS at SP6 induced increased FC between the left amygdala and brainstem, right hippocampus, and decreased FC between the left amygdala and left thalamus, bilateral supplementary motor area (SMA). Moreover, the results also showed that EAS at SP6 induced increased FC between the right amygdala and brainstem, right hippocampus, right orbitofrontal cortex, bilateral anterior cingulate cortex (ACC), and decreased FC between the right amygdala and right SMA. Conclusions: Based on the results of our previous study, our findings might improve our understanding of neural mechanisms behind acupuncture effects on PMS.

Changes in the neural correlates of self-blame following mindfulness-based cognitive therapy in remitted depressed participants.

Mindfulness-Based-Cognitive-Therapy (MBCT) reduces vulnerability for relapse into depression by helping individuals to counter tendencies to engage in maladaptive repetitive patterns of thinking and respond more compassionately to negative self-judgment. However, little is known about the neural correlates underlying these effects. To elucidate these correlates, we investigated fMRI brain activation during a task eliciting feelings of blaming oneself or others. Sixteen participants in remission from major depressive disorder (MDD) completed fMRI assessments before and after MBCT, alongside self-reported levels of self-compassion, mindfulness, and depression symptoms. Analyses of self-blame versus other-blame contrasts showed a reduction in activation in the bilateral dorsal anterior cingulate/medial superior frontal gyrus after MBCT compared to baseline. Further, exploratory analyses showed that increases in self-kindness after MBCT correlated with reduced activation in the posterior cingulate cortex (PCC)/precuneus in self-blame versus rest contrasts. These findings suggest that MBCT is associated with a reduction in activations in cortical midline regions to self-blame which may be mediated by increasing self-kindness. However, this is a small, uncontrolled study with 16 participants and therefore our results will need confirmation in a controlled study.

Functional disruption in prefrontal-striatal network in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. While a cortico-striatal-limbic network has been implicated in the pathophysiology of OCD, the neural correlates of this network in OCD are not well understood. In this study, we examined resting state functional connectivity among regions within the cortico-striatal-limbic OCD neural network, including the rostral anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, thalamus and caudate, in 44 OCD and 43 healthy participants. We then examined relationships between OCD neural network connectivity and OCD symptom severity in OCD participants. OCD relative to healthy participants showed significantly greater connectivity between the left caudate and bilateral dorsolateral prefrontal cortex. We also found a positive correlation between left caudate-bilateral dorsolateral prefrontal cortex connectivity and depression scores in OCD participants, such that greater positive connectivity was associated with more severe symptoms. This study makes a significant contribution to our understanding of functional networks and their relationship with depression in OCD.

Central Nervous System Reorganization and Pain After Spinal Cord Injury: Possible Targets for Physical Therapy-A Systematic Review of Neuroimaging Studies.

BACKGROUND: Pain is one of the main symptoms associated with spinal cord injury (SCI) and can be associated with changes to the central nervous system (CNS). PURPOSE: This article provides an overview of the evidence relating to CNS changes (structural and functional) associated with pain in SCIs. DATA SOURCES: A systematic review was performed, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on PubMed, Embase, and Web of Science in March 2018. STUDY SELECTION: Studies were selected if they concerned changes in the CNS of patients with SCI, regardless of the type of imagery. DATA EXTRACTION: Data were extracted by 2 blinded reviewers. DATA SYNTHESIS: There is moderate evidence for impaired electroencephalographic function and metabolic abnormalities in the anterior cingulate in patients experiencing pain. There is preliminary evidence that patients with pain have morphological and functional changes to the somatosensory cortex and alterations to thalamic metabolism. There are conflicting data regarding the relationships between lesion characteristics and pain. In contrast, patients without pain can display protective neuroplasticity. LIMITATIONS AND CONCLUSION: Further studies are required to elucidate fully the relationships between pain and neuroplasticity in patients with SCIs. However, current evidence might support the use of physical therapist treatments targeting CNS plasticity in patients with SCI pain.

Hyperactivated PTP1B phosphatase in parvalbumin neurons alters anterior cingulate inhibitory circuits and induces autism-like behaviors.

Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulty filtering information. Inhibitory interneurons filter information at pyramidal neurons of the anterior cingulate cortex (ACC), an integration hub for higher-order thalamic inputs important for social interaction. Humans with deletions including LMO4, an endogenous inhibitor of PTP1B, display intellectual disabilities and occasionally autism. PV-Lmo4KO mice ablate Lmo4 in PV interneurons and display ASD-like repetitive behaviors and social interaction deficits. Surprisingly, increased PV neuron-mediated peri-somatic feedforward inhibition to the pyramidal neurons causes a compensatory reduction in (somatostatin neuron-mediated) dendritic inhibition. These homeostatic changes increase filtering of mediodorsal-thalamocortical inputs but reduce filtering of cortico-cortical inputs and narrow the range of stimuli ACC pyramidal neurons can distinguish. Simultaneous ablation of PTP1B in PV-Lmo4KO neurons prevents these deficits, indicating that PTP1B activation in PV interneurons contributes to ASD-like characteristics and homeostatic maladaptation of inhibitory circuits may contribute to deficient information filtering in ASD.

Using connectivity-based real-time fMRI neurofeedback to modulate attentional and resting state networks in people with high trait anxiety.

High levels of trait anxiety are associated with impaired attentional control, changes in brain activity during attentional control tasks and altered network resting state functional connectivity (RSFC). Specifically, dorsolateral prefrontal cortex to anterior cingulate cortex (DLPFC - ACC) functional connectivity, thought to be crucial for effective and efficient attentional control, is reduced in high trait anxious individuals. The current study examined the potential of connectivity-based real-time functional magnetic imaging neurofeedback (rt-fMRI-nf) for enhancing DLPFC - ACC functional connectivity in trait anxious individuals. We specifically tested if changes in DLPFC - ACC connectivity were associated with reduced anxiety levels and improved attentional control. Thirty-two high trait anxious participants were assigned to either an experimental group (EG), undergoing veridical rt-fMRI-nf, or a control group (CG) that received sham (yoked) feedback. RSFC (using resting state fMRI), anxiety levels and Stroop task performance were assessed pre- and post-rt-fMRI-nf training. Post-rt-fMRI-nf training, relative to the CG, the EG showed reduced anxiety levels and increased DLPFC-ACC functional connectivity as well as increased RSFC in the posterior default mode network. Moreover, in the EG, changes in DLPFC - ACC functional connectivity during rt-fMRI-nf training were associated with reduced anxiety levels. However, there were no group differences in Stroop task performance. We conclude that rt-fMRI-nf targeting DLPFC - ACC functional connectivity can alter network connectivity and interactions and is a feasible method for reducing trait anxiety.

Brain activation patterns of female multiple sclerosis patients with voiding dysfunction.

AIMS: We compared brain activation patterns between female multiple sclerosis (MS) patients with voiding dysfunction (VD) and those without. We aim to expand current knowledge of supraspinal correlates of voiding initiation within a cohort of female MS patients with and without VD. MATERIALS AND METHODS: Twenty-eight ambulatory female MS patients with stable disease and lower urinary tract dysfunction were recruited for this study. Subjects were divided into group 1, without VD (n = 14), and group 2, with VD (n = 14), defined as postvoid residual urine of ≥40% of maximum cystometric capacity or need for self-catheterization. We recorded brain activity via functional magnetic resonance imaging (fMRI) with simultaneous urodynamic testing. Average fMRI activation maps (the Student t test) were created for both groups, and areas of significant activation were identified (P < .05). A priori regions of interest (ROIs), identified by prior meta-analysis to be involved in voiding, were selected. RESULTS: Group-averaged blood-oxygen level-dependent (BOLD) activation maps demonstrated significant differences between groups 1 and 2 during initiation of voiding with group 2 showing significantly lower levels of activation in all ROIs except for the left cerebellum and right cingulate gyrus. Interestingly, group 2 displayed negative BOLD signals, while group 1 displayed positive signals in the right and left pontine micturition center, right periaqueductal gray, left thalamus, and left cingulate gyrus. The activation map of group 1 was similar to healthy controls. CONCLUSIONS: Our results support the hypothesis that distinct supraspinal activation patterns exist between female MS patients with VD and those without.

Convergent neural representations of experimentally-induced acute pain in healthy volunteers: A large-scale fMRI meta-analysis.

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute nociceptive pain.

Changes in resting-state functional connectivity in nonacute sciatica with acupuncture modulation: A preliminary study.

AIMS: To investigate the functional connectivity (FC) in nonacute sciatica and the neuronal correlation of acupuncture analgesia. METHODS: A prospective study employing resting-state functional magnetic resonance imaging was conducted. Twelve sciatica patients were enrolled to receive six or 18 acupoints of acupuncture treatment twice a week for 4 weeks. Regional homogeneity (ReHo) and seed-based FC were performed. RESULTS: Regional homogeneity analysis demonstrated a greater alteration in the right posterior cingulate cortex (PCC) during the pre-acupuncture phase than during the postacupuncture phase. Compared to that of healthy controls, the PCC-seeded FC (default mode network, DMN) of sciatica patients exhibited hyperconnectivity of PCC-FC with the PCC-bilateral insula, cerebellum, inferior parietal lobule, right medial prefrontal cortex, and dorsal anterior cingulate cortex during the pre-acupuncture phase as well as hypoconnectivity of PCC-FC with the right cerebellum, left precuneus, and left dorsal medial prefrontal cortex during the postacupuncture phase. Correlation analysis between PCC-seeded FC and behavior measurements revealed a positive association with the duration of sciatica in the right inferior parietal lobule prior to acupuncture treatment. CONCLUSIONS: Acupuncture in chronic sciatica patients is associated with normalized DMN activity and modulation of descending pain processing. The changes in the subclinical endophenotype of brain FC after acupuncture treatment may provide clues for understanding the mechanism of acupuncture-mediated analgesia in chronic pain.

Eliciting Smiles and Laughter During Intraoperative Electric Stimulation of the Cingulum: Surgical Scenario.

Laughter has a major role in daily social interactions; consequently, its biologic bases have been previously studied. Nevertheless, its cerebral representation remains unclear. The most accepted hypothesis has postulated that laughter has 2 components: mirth, related to the temporal and frontal neocortical areas, and motor aspect, related to the limbic system and brainstem. Furthermore, in prior studies, laughter has been elicited during electric stimulation with depth electrodes in the supplementary motor area and the cingulum. This Video 1 reports resection of a right superior frontal gyrus diffuse astrocytoma (isocitrate dehydrogenase mutant, World Health Organization grade II) with awake intraoperative electric cortical and subcortical stimulation mapping. Diffusion tensor imaging (DTI) tractography, including all the tracts in relation to the tumor, was obtained preoperatively and postoperatively. Stimulation of the cingulum medially and inferiorly to the tumor elicited a patient's smile and laugh without mirth or merriment. Also, this point correlated with the reconstructed cingulum in the intraoperatively navigated DTI tractography. In conclusion, these findings support the anatomic subdivision of the laughter's mechanism and the role of the cingulum in its motor component. Furthermore, smiles and laughter could be useful functional landmarks to identify the cingulum during subcortical mapping. Although it remains unclear whether pursuing resection beyond this point would have caused permanent postoperative deficits, considering laughter's role in social interaction and other emotion-processing functions associated with the cingulum, in the future it could be potentially considered a functional limit of the resection of intrinsic tumors.

Alterations of functional connectivity between thalamus and cortex before and after decompression in cervical spondylotic myelopathy patients: a resting-state functional MRI study.

OBJECTIVE: Cervical spondylotic myelopathy is regarded as a chronic, special incomplete spinal cord injury, so the sensory components transmitted to thalamus decreased after distal spinal cord injury, which lead the disturbance of thalamus-cortex circuits, which might explain the alterations of clinical function of cervical spondylotic myelopathy patients. However, for lack of effective methods to evaluate the disturbance circuits and how the relative mechanism adapt to the recovery of cervical spondylotic myelopathy patients after decompression. Therefore, this study aim to explore how the possible mechanism of thalamus-cortex circuits reorganization adapt to the recovery of clinical function. METHODS: Regard thalamus as the interest area, we evaluate the brain functional connectivity within 43 pre-operative cervical spondylotic myelopathy patients, 21 post-operative (after 3 months) cervical spondylotic myelopathy patients and 43 healthy controls. Functional connectivity difference between pre-/post-operative cervical spondylotic myelopathy group and healthy controls group were obtained by two independent samples t-test, and difference between pre-operative cervical spondylotic myelopathy and post-operative cervical spondylotic myelopathy group were obtained by paired t-test. Clinical function was measured via Neck Disability Index and Japanese Orthopaedic Association scores. Furthermore, Pearson correlation were used to analyse the correlation between functional connectivity values and clinical scores. RESULTS: Compared with healthy controls group, pre-operative cervical spondylotic myelopathy group showed increased functional connectivity between left thalamus and bilateral lingual gyrus/cuneus/right cerebellum posterior lobe (Voxel P-value <0.01, Cluster P-value <0.05, GRF corrected); post-operative cervical spondylotic myelopathy group manifested decreased functional connectivity between right thalamus and bilateral paracentral lobe/precentral gyrus but significantly increased between right thalamus and pons/superior temporal gyrus. In comparison with pre-operative cervical spondylotic myelopathy group, post-operative cervical spondylotic myelopathy group showed increased functional connectivity between bilateral thalamus and posterior cingulate lobe, angular gyrus, medial prefrontal, but significantly decreased functional connectivity between bilateral thalamus and paracentral lobe/precentral gyrus. The functional connectivity between left thalamus and bilateral lingual gyrus/cuneus/right cerebellum posterior lobe in pre-operative cervical spondylotic myelopathy group have a significantly positive correlation with sensory Japanese Orthopaedic Association scores (r = 0.568, P < 0.001). The functional connectivity between thalamus and paracentral lobe/precentral gyrus in post-operative cervical spondylotic myelopathy group have a significantly positive correlation with upper limb movement Japanese Orthopaedic Association scores (r = 0.448, P = 0.042). CONCLUSION: Pre- or post-operative cervical spondylotic myelopathy patients showed functional connectivity alteration between thalamus and cortex, which suggest adaptive changes may favor the preservation of cortical sensorimotor networks before and after cervical cord decompression, and supply the improvement of clinical function.

Neuroticism modulates neural activities of posterior cingulate cortex and thalamus during psychosocial stress processing.

OBJECTIVE: Individuals with higher neuroticism are vulnerable to stress and are prone to develop depression, however, the neural mechanisms underlying it have not been clarified clearly. METHOD: The Montreal Imaging Stress Task (MIST) was administered to 148 healthy adults during functional magnetic resonance imaging (fMRI). Whole-brain voxel-wise regression analyses were used to detect associations of neuroticism with neural activity involved in perceiving and processing psychosocial stress. In addition, two-sample t-tests were conducted between the high-neurotic and low-neurotic group in order to supplement the results found in regression analyses. RESULTS: Higher neuroticism scores were associated with higher activities in the posterior cingulate cortex (PCC)/precuneus and thalamus (p < 0.05, false discovery rate correction). Moreover, two sample t-tests also revealed that the high-neurotic group had higher neural stress responses in precuneus and bilateral thalamus in comparison to the low-neurotic group (p < 0.05, false discovery rate correction). LIMITATIONS: Our study mainly recruited young adults, which may limit the generalizability of our findings. CONCLUSIONS: Our findings highlight the crucial role of PCC/precuneus and thalamus in the association between neuroticism and stress and may provide insight into the cognitive model of depression.

Cingulate role in Tourette syndrome.

This chapter comprehensively reviews the published record for neurosurgical, neurostimulatory, and neuroimaging evidence of the involvement of the cingulate gyrus in Gilles de la Tourette syndrome (TS). The most noteworthy evidence comes from neuroimaging. Neuroimaging findings were rarely exclusive to the cingulate cortex and tended to implicate multiple other cortices as well. Some results are reflective of obsessive-compulsive (OC) symptoms of TS. Copious findings, however, drawn from structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), resting-state functional magnetic resonance imaging (rsfMRI), task fMRI, and positron emission tomography (PET) implicate six of the eight cingulate subregions in TS. Gauged by MRI, cortical thinning and/or below-normal volume are seen in subgenual anterior cingulate cortex (sACC), pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and posterior middle cingulate cortex (pMCC), correlating with tic severity in sACC, pACC, and aMCC. Moreover, in pMCC, dorsal posterior cingulate cortex (dPCC), and ventral posterior cingulate cortex (vPCC), cortical thickness is a candidate biomarker shared across siblings with TS. Loss of cortex may reflect excitotoxicity secondary to insufficient local GABAergic inhibition, a notion supported by the few relevant MRS and PET studies conducted to date, recommending continued development of GABAergic and glutamatergic pharmacologic agents to treat TS. Measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained with DTI indicate that the white matter proximal to sACC, pACC, pMCC, and dPCC may also represent a seat of pathology in TS. rsfMRI reveals abnormal functional connectivity of pACC and dPCC with the globus pallidus internus, a favored target of therapeutic deep brain stimulation (DBS) for TS. In whole-brain network (graph theory) analysis, dPCC functional connectivity is related to the severity and complexity of tics. In task fMRI, in contrast, the pMCC seems to play a preeminent role in premonitory urges and preparation for tics as well as normal urges to urinate, swallow, and yawn. Strong monkey PET and EEG evidence ties vocal tics to spike discharges, α-activity, and regional blood flow in the pACC unleashed by failure of GABAergic inhibition in the ventral striatum. Tic suppression in fMRI scans is associated with increased blood oxygenation level-dependent activity in sACC, pACC, and aMCC, but decreased activity in pMCC and dPCC. Activity in the former three subregions may represent volitional effort, physical discomfort, and emotional distress that accompanies mounting tic urges; pMCC and dPCC may be more instrumental in amplifying than suppressing urges. Needs for future neuroimaging work in TS include longitudinal studies-particularly those striving to predict which individual pediatric patients will continue to suffer from TS as adults and studies of treatment response-particularly of behavioral therapies, which are as efficacious as pharmacology. Transcranial magnetic stimulation and related therapies such as cranial electrotherapy stimulation, which showed good efficacy in a recent trial, merit continued exploration. TS research using DTI, MRS, and PET will no doubt continue to benefit in coming years from technological advances such as ultrahigh-field scanners, multichannel head coils, and novel (including GABAergic and glutamatergic) ligands.

Cingulate-basal ganglia-thalamo-cortical aspects of catatonia and implications for treatment.

The catatonic syndrome is an example of a multifactorial neurobehavioral disorder that causes much morbidity and mortality but also has the potential to unlock the mystery of how motivation and movement interact to produce behavior. In this chapter, an attempt is made to understand better the catatonic syndrome through the lens of neurobiology and neuropathophysiology updated by recent studies in molecular biology, genomics, inflammasomics, neuroimaging, neural network theory, and neuropsychopathology. This will result in a neurostructural model for the catatonic syndrome that centers on paralimbic regions including the anterior and midcingulate cortices, as they interface with striatal and thalamic nodes in the salience decision-making network. Examination of neurologic disorders like the abulic syndrome, which includes in its extreme catatonic form, akinetic mutism, will identify the cingulate cortex and paralimbic neighbors as regions of interest. This exploration has the potential to unlock mysteries of the brain cascade from motivation to movement and to clarify catatonia therapeutics. Such a synthesis may also help us discern meaning inherent in this complex neurobehavioral syndrome.