Acupuncture for Parkinson's Disease: Efficacy Evaluation and Mechanisms in the Dopaminergic Neural Circuit.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.

Effect of Acupuncture on Neuroplasticity of Stroke Patients with Motor Dysfunction: A Meta-Analysis of fMRI Studies.

Objective: To analyze the pattern of intrinsic brain activity variability that is altered by acupuncture compared with conventional treatment in stroke patients with motor dysfunction, thus providing the mechanism of stroke treatment by acupuncture. Methods: Chinese and English articles published up to May 2020 were searched in the PubMed, Web of Science, EMBASE, and Cochrane Library databases, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang Database. We only included randomized controlled trials (RCTs) using resting-state fMRI to observe the effect of acupuncture on stroke patients with motor dysfunction. R software was used to analyze the continuous variables, and Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) was used to perform an analysis of fMRI data. Findings. A total of 7 studies comprising 143 patients in the treatment group and 138 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps the healing process of motor dysfunction in stroke patients and exhibits hyperactivation in the bilateral basal ganglia and insula and hypoactivation in motor-related areas (especially bilateral BA6 and left BA4). Conclusion: Acupuncture plays a role in promoting neuroplasticity in subcortical regions that are commonly affected by stroke and cortical motor areas that may compensate for motor deficits, which may provide a possible mechanism underlying the therapeutic effect of acupuncture.

Resting-state functional connectivity associated with gait characteristics in people with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a movement disorder caused by dysfunction in the basal ganglia (BG). Clinically relevant gait deficits, such as decreased velocity and increased variability, may be caused by underlying neural dysfunction. Reductions in resting-state functional connectivity (rs-FC) between networks have been identified in PD compared to controls; however, the association between gait characteristics and rs-FC of brain networks in people with PD has not yet been explored. The present study aimed to investigate these associations. METHODS: Gait characteristics and rs-FC MRI data were collected for participants with PD (N = 50). Brain networks were identified from a set of seeds representing cortical, subcortical, and cerebellar regions. Gait outcomes were correlated with the strength of rs-FC within and between networks of interest. A stepwise regression analysis was also conducted to determine whether the rs-FC strength of brain networks, along with clinical motor scores, were predictive of gait characteristics. RESULTS: Gait velocity was associated with rs-FC within the visual network and between motor and cognitive networks, most notably BG-thalamus internetwork rs-FC. The stepwise regression analysis showed strength of BG-thalamus internetwork rs-FC and clinical motor scores were predictive of gait velocity. CONCLUSION: The results of the present study demonstrate gait characteristics are associated with functional organization of the brain at the network level, providing insight into the neural mechanisms of clinically relevant gait characteristics. This knowledge could be used to optimize the design of gait rehabilitation interventions for people with neurological conditions.

Distinct effects of the basal ganglia and cerebellum on the thalamocortical pathway in idiopathic generalized epilepsy.

The aberrant thalamocortical pathways of epilepsy have been detected recently, while its underlying effects on epilepsy are still not well understood. Exploring pathoglytic changes in two important thalamocortical pathways, that is, the basal ganglia (BG)-thalamocortical and the cerebellum-thalamocortical pathways, in people with idiopathic generalized epilepsy (IGE), could deepen our understanding on the pathological mechanism of this disease. These two pathways were reconstructed and investigated in this study by combining diffusion and functional MRI. Both pathways showed connectivity changes with the perception and cognition systems in patients. Consistent functional connectivity (FC) changes were observed mainly in perception regions, revealing the aberrant integration of sensorimotor and visual information in IGE. The pathway-specific FC alterations in high-order regions give neuroimaging evidence of the neural mechanisms of cognitive impairment and epileptic activities in IGE. Abnormal functional and structural integration of cerebellum, basal ganglia and thalamus could result in an imbalance of inhibition and excitability in brain systems of IGE. This study located the regulated cortical regions of BG and cerebellum which been affected in IGE, established possible links between the neuroimaging findings and epileptic symptoms, and enriched the understanding of the regulatory effects of BG and cerebellum on epilepsy.

Functional Role of the Cerebellum in Parkinson Disease: A PET Study.

OBJECTIVES: To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism. METHODS: We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations. RESULTS: Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters. CONCLUSIONS: These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops.

The Ictal Signature of Thalamus and Basal Ganglia in Focal Epilepsy: A SEEG Study.

OBJECTIVE: To determine the involvement of subcortical regions in human epilepsy by analyzing direct recordings from these regions during epileptic seizures using stereo-EEG (SEEG). METHODS: We studied the SEEG recordings of a large series of patients (74 patients, 157 seizures) with an electrode sampling the thalamus and in some cases also the basal ganglia (caudate nucleus, 22 patients; and putamen, 4 patients). We applied visual analysis and signal quantification methods (Epileptogenicity Index [EI]) to their ictal recordings and compared electrophysiologic with clinical data. RESULTS: We found that in 86% of patients, thalamus was involved during seizures (visual analysis) and 20% showed high values of epileptogenicity (EI >0.3). Basal ganglia may also disclose high values of epileptogenicity (9% in caudate nucleus) but to a lesser degree than thalamus (p < 0.01). We observed different seizure onset patterns including low voltage high frequency activities. We found high values of thalamic epileptogenicity in different epilepsy localizations, including opercular and motor epilepsies. We found no difference between epilepsy etiologies (cryptogenic vs malformation of cortical development, p = 0.77). Thalamic epileptogenicity was correlated with the extension of epileptogenic networks (p = 0.02, ρ 0.32). We found a significant effect (p < 0.05) of thalamic epileptogenicity regarding the postsurgical outcome (higher thalamic EI corresponding to higher probability of surgical failure). CONCLUSIONS: Thalamic involvement during seizures is common in different seizure types. The degree of thalamic epileptogenicity is a possible marker of the epileptogenic network extension and of postsurgical prognosis.

Local and large-scale beta oscillatory dysfunction in males with mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is impossible to detect with standard neuroradiological assessment such as structural magnetic resonance imaging (MRI). Injury does, however, disrupt the dynamic repertoire of neural activity indexed by neural oscillations. In particular, beta oscillations are reliable predictors of cognitive, perceptual, and motor system functioning, as well as correlating highly with underlying myelin architecture and brain connectivity-all factors particularly susceptible to dysregulation after mTBI. We measured local and large-scale neural circuit function by magnetoencephalography (MEG) with a data-driven model fit approach using the fitting oscillations and one-over f algorithm in a group of young adult men with mTBI and a matched healthy control group. We quantified band-limited regional power and functional connectivity between brain regions. We found reduced regional power and deficits in functional connectivity across brain areas, which pointed to the well-characterized thalamocortical dysconnectivity associated with mTBI. Furthermore, our results suggested that beta functional connectivity data reached the best mTBI classification performance compared with regional power and symptom severity [measured with Sport Concussion Assessment Tool 2 (SCAT2)]. The present study reveals the relevance of beta oscillations as a window into neurophysiological dysfunction in mTBI and also highlights the reliability of neural synchrony biomarkers in disorder classification.NEW & NOTEWORTHY Mild traumatic brain injury (mTBI) disrupts the dynamic repertoire of neural oscillations, but so far beta activity has not been studied. In mTBI, we found reductions in frontal beta and large-scale beta networks, indicative of thalamocortical dysconnectivity and disrupted information flow through cortico-basal ganglia-thalamic circuits. Relatively, connectivity more accurately classifies individual mTBI cases compared with regional power. We show the relevance of beta oscillations in mTBI and the reliability of these markers in classification.

Extrapyramidal plasticity predicts recovery after spinal cord injury.

Spinal cord injury (SCI) leads to wide-spread neurodegeneration across the neuroaxis. We explored trajectories of surface morphology, demyelination and iron concentration within the basal ganglia-thalamic circuit over 2 years post-SCI. This allowed us to explore the predictive value of neuroimaging biomarkers and determine their suitability as surrogate markers for interventional trials. Changes in markers of surface morphology, myelin and iron concentration of the basal ganglia and thalamus were estimated from 182 MRI datasets acquired in 17 SCI patients and 21 healthy controls at baseline (1-month post injury for patients), after 3, 6, 12, and 24 months. Using regression models, we investigated group difference in linear and non-linear trajectories of these markers. Baseline quantitative MRI parameters were used to predict 24-month clinical outcome. Surface area contracted in the motor (i.e. lower extremity) and pulvinar thalamus, and striatum; and expanded in the motor thalamus and striatum in patients compared to controls over 2-years. In parallel, myelin-sensitive markers decreased in the thalamus, striatum, and globus pallidus, while iron-sensitive markers decreased within the left caudate. Baseline surface area expansions within the striatum (i.e. motor caudate) predicted better lower extremity motor score at 2-years. Extensive extrapyramidal neurodegenerative and reorganizational changes across the basal ganglia-thalamic circuitry occur early after SCI and progress over time; their magnitude being predictive of functional recovery. These results demonstrate a potential role of extrapyramidal plasticity during functional recovery after SCI.

Tremor pathophysiology: lessons from neuroimaging.

PURPOSE OF REVIEW: We discuss the latest neuroimaging studies investigating the pathophysiology of Parkinson's tremor, essential tremor, dystonic tremor and Holmes tremor. RECENT FINDINGS: Parkinson's tremor is associated with increased activity in the cerebello-thalamo-cortical circuit, with interindividual differences depending on the clinical dopamine response of the tremor. Although dopamine-resistant Parkinson's tremor arises from a larger contribution of the (dopamine-insensitive) cerebellum, dopamine-responsive tremor may be explained by thalamic dopamine depletion. In essential tremor, deep brain stimulation normalizes cerebellar overactivity, which fits with the cerebellar oscillator hypothesis. On the other hand, disconnection of the dentate nucleus and abnormal white matter microstructural integrity support a decoupling of the cerebellum in essential tremor. In dystonic tremor, there is evidence for involvement of both cerebellum and basal ganglia, although this may depend on the clinical phenotype. Finally, in Holmes tremor, different causal lesions map to a common network consisting of the red nucleus, internal globus pallidus, thalamus, cerebellum and pontomedullary junction. SUMMARY: The pathophysiology of all investigated tremors involves the cerebello-thalamo-cortical pathway, and clinical and pathophysiological features overlap among tremor disorders. We draw the outlines of a hypothetical pathophysiological axis, which may be used besides clinical features and cause in future tremor classifications.

Basal ganglia oscillations as biomarkers for targeting circuit dysfunction in Parkinson's disease.

Oscillations are a naturally occurring phenomenon in highly interconnected dynamical systems. However, it is thought that excessive synchronized oscillations in brain circuits can be detrimental for many brain functions by disrupting neuronal information processing. Because synchronized basal ganglia oscillations are a hallmark of Parkinson's disease (PD), it has been suggested that aberrant rhythmic activity associated with symptoms of the disease could be used as a physiological biomarker to guide pharmacological and electrical neuromodulatory interventions. We here briefly review the various manifestations of basal ganglia oscillations observed in human subjects and in animal models of PD. In this context, we also review the evidence supporting a pathophysiological role of different oscillations for the suppression of voluntary movements as well as for the induction of excessive motor activity. In light of these findings, it is discussed how oscillations could be used to guide a more precise targeting of dysfunctional circuits to obtain improved symptomatic treatment of PD.

Enhanced positive functional connectivity strength in left-sided chronic subcortical stroke.

Patients with stroke often exhibit evidence of abnormal functional connectivity (FC). However, whether and how anatomical distance affects FC at rest remains unclear in patients with chronic subcortical stroke. Eighty-six patients with chronic (more than six months post-onset) subcortical stroke (44 left-sided patients and 42 right-sided patients) with different degrees of functional recovery, and 75 matched healthy controls underwent resting-state functional magnetic resonance imaging scanning. Positive functional connectivity strength (FCS) was computed for each voxel in the brain using a data-driven whole-brain resting state FCS method, which was further divided into short- and long-range FCS. Compared with healthy controls, patients with left-sided infarctions exhibited stronger global- and long-range FCS in the left sensorimotor cortex (SMC), and no significant intergroup difference was found for short-range FCS. No significant differences were found between the patients with right-sided infarctions and healthy controls for global, long- and short-range FCS. These findings suggested that the positive FCS alteration was connection-distance dependent within patients with left-sided chronic subcortical stroke. Also, a positive correlation was found between the FCS in the left SMC and the accuracy of the Flanker test, reflecting a compensatory FCS alteration for altered attention and executive function abilities exhibited by those with left-sided stroke.

Functional disconnection of the dentate nucleus in essential tremor.

Despite previous functional MRI studies on alterations within the cerebello-thalamo-cortical circuit in patients with essential tremor (ET), the specific role of disconnection of the dentate nucleus (DN), the main output cerebellar pathway, still needs clarification. In this study, we evaluated DN functional connectivity (FC) changes and their relationship with motor and non-motor symptoms in ET. We studied 25 ET patients and 26 healthy controls. Tremor severity was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and tremor amplitude and frequency were evaluated using kinematic techniques. Cognitive profile was assessed by montreal cognitive assessment (MoCA) and frontal assessment battery (FAB). All participants underwent a 3 T MRI protocol including resting-state blood oxygenation level dependent and diffusion tensor sequences. We used a seed-based approach to investigate DN FC and to explore the diffusion properties of cerebellar peduncles. There was significantly decreased DN FC with cortical, subcortical, and cerebellar areas in ET patients compared with healthy controls. Correlation analysis showed that: (1) the DN FC with the supplementary motor area, pre and postcentral gyri, and prefrontal cortex negatively correlated with FTM-TRS score and disease duration; (2) DN FC changes in the thalamus and caudate negatively correlated with peak tremor frequency, changes in the cerebellum positively correlated with tremor amplitude, and changes in the bilateral thalamus negatively correlated with tremor amplitude, and (3) DN FC with the associative prefrontal and parietal cortices, basal ganglia, and thalamus positively correlated with the MoCA score. Diffusion abnormalities were found in the three cerebellar peduncles, which did not correlate with clinical scores.

The role of coupling connections in a model of the cortico-basal ganglia-thalamocortical neural loop for the generation of beta oscillations.

Excessive neural synchronization in the cortico-basal ganglia-thalamocortical circuits in the beta (ß) frequency range (12-35 Hz) is closely associated with dopamine depletion in Parkinson's disease (PD) and correlated with movement impairments, but the neural basis remains unclear. In this work, we establish a double-oscillator neural mass model for the cortico-basal ganglia-thalamocortical closed-loop system and explore the impacts of dopamine depletion induced changes in coupling connections within or between the two oscillators on neural activities within the loop. Spectral analysis of the neural mass activities revealed that the power and frequency of their principal components are greatly dependent on the coupling strengths between nuclei. We found that the increased intra-coupling in the basal ganglia-thalamic (BG-Th) oscillator contributes to increased oscillations in the lower ß frequency band (12-25 Hz), while increased intra-coupling in the cortical oscillator mainly contributes to increased oscillations in the upper ß frequency band (26-35 Hz). Interestingly, pathological upper ß oscillations in the cortical oscillator may be another origin of the lower ß oscillations in the BG-Th oscillator, in addition to increased intra-coupling strength within the BG-Th network. Lower ß oscillations in the BG-Th oscillator can also change the dominant oscillation frequency of a cortical nucleus from the upper to the lower ß band. Thus, this work may pave the way towards revealing a possible neural basis underlying the Parkinsonian state.

Functional, Anatomical, and Morphological Networks Highlight the Role of Basal Ganglia-Thalamus-Cortex Circuits in Schizophrenia.

Evidence from electrophysiological, functional, and structural research suggests that abnormal brain connectivity plays an important role in the pathophysiology of schizophrenia. However, most previous studies have focused on single modalities only, each of which is associated with its own limitations. Multimodal combinations can more effectively utilize various information, but previous multimodal research mostly focuses on extracting local features, rather than carrying out research based on network perspective. This study included 135 patients with schizophrenia and 148 sex- and age-matched healthy controls. Functional magnetic resonance imaging, diffusion tensor imaging, and structural magnetic resonance imaging data were used to construct the functional, anatomical, and morphological networks of each participant, respectively. These networks were used in combination with machine learning to identify more consistent biomarkers of brain connectivity and explore the relationships between different modalities. We found that although each modality had divergent connectivity biomarkers, the convergent pattern was that all were mostly located within the basal ganglia-thalamus-cortex circuit. Furthermore, using the biomarkers of these 3 modalities as a feature yielded the highest classification accuracy (91.75%, relative to a single modality), suggesting that the combination of multiple modalities could be effectively utilized to obtain complementary information regarding different mode networks; furthermore, this information could help distinguish patients. These findings provide direct evidence for the disconnection hypothesis of schizophrenia, suggesting that abnormalities in the basal ganglia-thalamus-cortex circuit can be used as a biomarker of schizophrenia.

Application of Reinforcement Learning to Deep Brain Stimulation in a Computational Model of Parkinson's Disease.

Deep brain stimulation (DBS) has been proven to be an effective treatment to deal with the symptoms of Parkinson's disease (PD). Currently, the DBS is in an open-loop pattern with which the stimulation parameters remain constant regardless of fluctuations in the disease state, and adjustments of parameters rely mostly on trial and error of experienced clinicians. This could bring adverse effects to patients due to possible overstimulation. Thus closed-loop DBS of which stimulation parameters are automatically adjusted based on variations in the ongoing neurophysiological signals is desired. In this paper, we present a closed-loop DBS method based on reinforcement learning (RL) to regulate stimulation parameters based on a computational model. The network model consists of interconnected biophysically-based spiking neurons, and the PD state is described as distorted relay reliability of thalamus (TH). Results show that the RL-based closed-loop control strategy can effectively restore the distorted relay reliability of the TH but with less DBS energy expenditure.

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

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.

Alterations in basal ganglia-cerebello-thalamo-cortical connectivity and whole brain functional network topology in Tourette's syndrome.

Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by the presence of motor and vocal tics. Major pathophysiological theories posit a dysfunction of the cortico-striato-thalamo-cortical circuits as being a representative hallmark of the disease. Recent evidence suggests a more widespread dysfunction of brain networks in TS including the cerebellum and going even beyond classic motor pathways. In order to characterize brain network dysfunction in TS, in this study we investigated functional and effective-like connectivity as well as topological changes of basal ganglia-thalamo-cortical and cortico-cerebellar brain networks. We collected resting-state fMRI data from 28 TS patients (age: 32 ±â€¯11 years) and 28 age-matched, healthy controls (age: 31 ±â€¯9 years). Region of interest based (ROI-ROI) bivariate correlation and ROI-ROI bivariate regression were employed as measures of functional and effective-like connectivity, respectively. Graph theoretical measures of centrality (degree, cost, betweenness centrality), functional segregation (clustering coefficient, local efficiency) and functional integration (average path length, global efficiency) were used to assess topological brain network changes. In this study, TS patients exhibited increased basal ganglia-cortical and thalamo-cortical connectivity, reduced cortico-cerebellar connectivity, and an increase in parallel communication through the basal ganglia, thalamus and cerebellum (increased global efficiency). Additionally, we observed a reduction in serial information transfer (reduction in average path length) within the default mode and the salience network. In summary, our findings show that TS is characterized by increased connectivity and functional integration of multiple basal ganglia-thalamo-cortical circuits, suggesting a predominance of excitatory neurotransmission and a lack of brain maturation. Moreover, topological changes of cortico-cerebellar and brain networks involved in interoception may be underestimated neural correlates of tics and the crucial premonitory urge feeling.

Cerebral differences between dopamine-resistant and dopamine-responsive Parkinson's tremor.

Rest tremor in Parkinson's disease is related to cerebral activity in both the basal ganglia and a cerebello-thalamo-cortical circuit. Clinically, there is strong interindividual variation in the therapeutic response of tremor to dopaminergic medication. This observation casts doubt on the idea that Parkinson's tremor has a dopaminergic basis. An interesting alternative explanation is that interindividual differences in the pathophysiology of tremor may underlie this clinical heterogeneity. Previous work showed that dopaminergic medication reduces Parkinson's tremor by inhibiting tremulous activity in the pallidum and thalamus, and this may explain why some tremors are dopamine-responsive. Here we test the hypothesis that dopamine-resistant resting tremor may be explained by increased contributions of non-dopaminergic brain regions, such as the cerebellum. To test this hypothesis, we first performed a levodopa challenge test in 83 tremulous Parkinson's disease patients, and selected 20 patients with a markedly dopamine-responsive tremor (71% reduction) and 14 patients with a markedly dopamine-resistant tremor (6% reduction). The dopamine response of other core motor symptoms was matched between groups. Next, in all 34 patients, we used combined EMG-functional MRI to quantify tremor-related brain activity during two separate sessions (crossover, double-blind, counterbalanced design): after placebo, or after 200/50 mg dispersible levodopa/benserazide. We compared tremor-related brain activity between groups and medication sessions. Both groups showed tremor amplitude-related brain activity in a cerebello-thalamo-cortical circuit. Dopamine-resistant tremor patients showed increased tremor-related activity in non-dopaminergic areas (cerebellum), whereas the dopamine-responsive group showed increased tremor-related activity in the thalamus and secondary somatosensory cortex (across medication sessions). Levodopa inhibited tremor-related thalamic responses in both groups, but this effect was significantly greater in dopamine-responsive patients. These results suggest that dopamine-resistant tremor may be explained by increased cerebellar and reduced somatosensory influences onto the cerebellar thalamus, making this region less susceptible to the inhibitory effects of dopamine.

Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain.

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ±â€¯12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ±â€¯13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources.