Focal Brain Lesions Causing Acquired Amusia Map to a Common Brain Network.

Music is a universal human attribute. The study of amusia, a neurologic music processing deficit, has increasingly elaborated our view on the neural organization of the musical brain. However, lesions causing amusia occur in multiple brain locations and often also cause aphasia, leaving the distinct neural networks for amusia unclear. Here, we utilized lesion network mapping to identify these networks. A systematic literature search was carried out to identify all published case reports of lesion-induced amusia. The reproducibility and specificity of the identified amusia network were then tested in an independent prospective cohort of 97 stroke patients (46 female and 51 male) with repeated structural brain imaging, specifically assessed for both music perception and language abilities. Lesion locations in the case reports were heterogeneous but connected to common brain regions, including bilateral temporoparietal and insular cortices, precentral gyrus, and cingulum. In the prospective cohort, lesions causing amusia mapped to a common brain network, centering on the right superior temporal cortex and clearly distinct from the network causally associated with aphasia. Lesion-induced longitudinal structural effects in the amusia circuit were confirmed as reduction of both gray and white matter volume, which correlated with the severity of amusia. We demonstrate that despite the heterogeneity of lesion locations disrupting music processing, there is a common brain network that is distinct from the language network. These results provide evidence for the distinct neural substrate of music processing, differentiating music-related functions from language, providing a testable target for noninvasive brain stimulation to treat amusia.

Dietary Caffeine and Brain Dopaminergic Function in Parkinson Disease.

OBJECTIVE: This study was undertaken to investigate the effects of dietary caffeine intake on striatal dopamine function and clinical symptoms in Parkinson disease in a cross-sectional and longitudinal setting. METHODS: One hundred sixty-three early Parkinson disease patients and 40 healthy controls were investigated with [123I]FP-CIT single photon emission computed tomography, and striatal dopamine transporter binding was evaluated in association with the level of daily coffee consumption and clinical measures. After a median interval of 6.1 years, 44 patients with various caffeine consumption levels underwent clinical and imaging reexamination including blood caffeine metabolite profiling. RESULTS: Unmedicated early Parkinson disease patients with high coffee consumption had 8.3 to 15.4% lower dopamine transporter binding in all studied striatal regions than low consumers, after accounting for age, sex, and motor symptom severity. Higher caffeine consumption was further associated with a progressive decline in striatal binding over time. No significant effects of caffeine on motor function were observed. Blood analyses demonstrated a positive correlation between caffeine metabolites after recent caffeine intake and dopamine transporter binding in the ipsilateral putamen. INTERPRETATION: Chronic caffeine intake prompts compensatory and cumulative dopamine transporter downregulation, consistent with caffeine's reported risk reduction in Parkinson disease. However, this decline does not manifest in symptom changes. Transiently increased dopamine transporter binding after recent caffeine intake has implications for dopaminergic imaging guidelines. ANN NEUROL 2024;96:262-275.

Localization of stuttering based on causal brain lesions.

Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering. Here, we investigated the neuroanatomical substrate of stuttering using three independent datasets: (i) case reports from the published literature of acquired neurogenic stuttering following stroke (n = 20, 14 males/six females, 16-77 years); (ii) a clinical single study cohort with acquired neurogenic stuttering following stroke (n = 20, 13 males/seven females, 45-87 years); and (iii) adults with persistent developmental stuttering (n = 20, 14 males/six females, 18-43 years). We used the first two datasets and lesion network mapping to test whether lesions causing acquired stuttering map to a common brain network. We then used the third dataset to test whether this lesion-based network was relevant to developmental stuttering. In our literature dataset, we found that lesions causing stuttering occurred in multiple heterogeneous brain regions, but these lesion locations were all functionally connected to a common network centred around the left putamen, including the claustrum, amygdalostriatal transition area and other adjacent areas. This finding was shown to be specific for stuttering (PFWE < 0.05) and reproducible in our independent clinical cohort of patients with stroke-induced stuttering (PFWE < 0.05), resulting in a common acquired stuttering network across both stroke datasets. Within the common acquired stuttering network, we found a significant association between grey matter volume and stuttering impact for adults with persistent developmental stuttering in the left posteroventral putamen, extending into the adjacent claustrum and amygdalostriatal transition area (PFWE < 0.05). We conclude that lesions causing acquired neurogenic stuttering map to a common brain network, centred to the left putamen, claustrum and amygdalostriatal transition area. The association of this lesion-based network with symptom severity in developmental stuttering suggests a shared neuroanatomy across aetiologies.

Bodily Maps of Symptoms and Emotions in Parkinson's Disease.

BACKGROUND: Emotions are reflected in bodily sensations, and these reflections are abnormal in psychiatric conditions. However, emotion-related bodily sensations have not been studied in neurological disorders. OBJECTIVE: The aim of this study was to investigate whether Parkinson's disease (PD) is associated with altered bodily representations of emotions. METHODS: Symptoms and emotion-related sensations were investigated in 380 patients with PD and 79 control subjects, using a topographical self-report method, termed body sensation mapping. The bodily mapping data were analyzed with pixelwise generalized linear models and principal component analyses. RESULTS: Bodily maps of symptoms showed characteristic patterns of PD motor symptom distributions. Compared with control subjects, PD patients showed decreased parasternal sensation of anger, and longer PD symptom duration was associated with increased abdominal sensation of anger (PFWE < 0.05). The PD-related sensation patterns were abnormal across all basic emotions (P < 0.05). CONCLUSIONS: The results demonstrate altered bodily maps of emotions in PD, providing novel insight into the nonmotor effects of PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

No Efficacy with Noninvasive Brain Stimulation for Painful Legs and Moving Toes: A Case Report.

Introduction: Painful legs and moving toes (PLMT) is a rare neurological disorder characterized by neuropathic pain and involuntary movements in the lower limbs. The pathophysiological mechanisms are unclear, but central mechanisms might be involved, suggesting that noninvasive brain stimulation might be helpful. Thus far, no reports have been published on noninvasive brain stimulation to treat PLMT. Case Presentation: A 70-year-old female had a 1-year history of PLMT. After several unsuccessful medical attempts, the patient received repetitive transcranial magnetic stimulation and transcranial direct current stimulation to alleviate the pain and involuntary movements with no benefit. Conclusion: This is the first report on noninvasive brain stimulation in a PLMT patient. Although ineffective in our patient, noninvasive brain stimulation should be further studied in this often difficult to treat and debilitating syndrome.

Frontal white and gray matter abnormality in gambling disorder: A multimodal MRI study.

Background: Changes in brain structural connections appear to be important in the pathophysiology of substance use disorders, but their role in behavioral addictions, such as gambling disorder (GD), is unclear. GD also offers a model to study addiction mechanisms without pharmacological confounding factors. Here, we used multimodal MRI data to examine the integrity of white matter connections in individuals with GD. We hypothesized that the affected areas would be in the fronto-striatal-thalamic circuit. Methods: Twenty individuals with GD (mean age: 64 years, GD duration: 15.7 years) and 40 age- and sex-matched healthy controls (HCs) underwent detailed clinical examinations together with brain 3T MRI scans (T1, T2, FLAIR and DWI). White matter (WM) analysis involved fractional anisotropy and lesion load, while gray matter (GM) analysis included voxel- and surface-based morphometry. These measures were compared between groups, and correlations with GD-related behavioral characteristics were examined. Results: Individuals with GD showed reduced WM integrity in the left and right frontal parts of the corona radiata and corpus callosum (pFWE < 0.05). WM gambling symptom severity (SOGS score) was negatively associated to WM integrity in these areas within the left hemisphere (p < 0.05). Individuals with GD also exhibited higher WM lesion load in the left anterior corona radiata (pFWE < 0.05). GM volume in the left thalamus and GM thickness in the left orbitofrontal cortex were reduced in the GD group (pFWE < 0.05). Conclusions: Similar to substance addictions, the fronto-striatal-thalamic circuit is also affected in GD, suggesting that this circuitry may have a crucial role in addictions, independent of pharmacological substances.

Brain lesions causing parkinsonism versus seizures map to opposite brain networks.

Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and used the human connectome to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatial r = -0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific on a group level (spatial r = -0.51) and on an individual lesion level (average spatial r = -0.042; P < 0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatial r > 0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.

Brain lesions causing parkinsonism versus seizures map to opposite brain networks.

Recent epidemiological studies propose an association between parkinsonism and seizures, but the direction of this association is unclear. Focal brain lesions causing new-onset parkinsonism versus seizures may provide a unique perspective on the causal relationship between the two symptoms and involved brain networks. We studied lesions causing parkinsonism versus lesions causing seizures and utilized human connectome data to identify their connected brain networks. Brain networks for parkinsonism and seizures were compared using spatial correlations on a group and individual lesion level. Lesions not associated with either symptom were used as controls. Lesion locations from 29 patients with parkinsonism were connected to a brain network with the opposite spatial topography (spatial r =-0.85) compared to 347 patients with lesions causing seizures. A similar inverse relationship was found when comparing the connections that were most specific for lesions causing parkinsonism versus seizures on a group level (spatial r =- 0.51) and on an individual lesion level (average spatial r =-0.042; p<0.001). The substantia nigra was found to be most positively correlated to the parkinsonism network but most negatively correlated to the seizure network (spatial r >0.8). Brain lesions causing parkinsonism versus seizures map to opposite brain networks, providing neuroanatomical insight into conflicting epidemiological evidence.

Multimodal neuroimaging to characterize symptom-specific networks in movement disorders.

Movement disorders, such as Parkinson's disease, essential tremor, and dystonia, are characterized by their predominant motor symptoms, yet diseases causing abnormal movement also encompass several other symptoms, including non-motor symptoms. Here we review recent advances from studies of brain lesions, neuroimaging, and neuromodulation that provide converging evidence on symptom-specific brain networks in movement disorders. Although movement disorders have traditionally been conceptualized as disorders of the basal ganglia, cumulative data from brain lesions causing parkinsonism, tremor and dystonia have now demonstrated that this view is incomplete. Several recent studies have shown that lesions causing a given movement disorder occur in heterogeneous brain locations, but disrupt common brain networks, which appear to be specific to each motor phenotype. In addition, findings from structural and functional neuroimaging in movement disorders have demonstrated that brain abnormalities extend far beyond the brain networks associated with the motor symptoms. In fact, neuroimaging findings in each movement disorder are strongly influenced by the constellation of patients' symptoms that also seem to map to specific networks rather than individual anatomical structures or single neurotransmitters. Finally, observations from deep brain stimulation have demonstrated that clinical changes, including both symptom improvement and side effects, are dependent on the modulation of large-scale networks instead of purely local effects of the neuromodulation. Combined, this multimodal evidence suggests that symptoms in movement disorders arise from distinct brain networks, encouraging multimodal imaging studies to better characterize the underlying symptom-specific mechanisms and individually tailor treatment approaches.

Current opinions and practices in post-stroke movement disorders: Survey of movement disorders society members.

BACKGROUND: Post-stroke movement disorders (PSMD) encompass a wide array of presentations, which vary in mode of onset, phenomenology, response to treatment, and natural history. There are no evidence-based guidelines on the diagnosis and treatment of PSMD. OBJECTIVES: To survey current opinions and practices on the diagnosis and treatment of PSMD. METHODS: A survey was developed by the PSMD Study Group, commissioned by the International Parkinson's and Movement Disorders Society (MDS). The survey, distributed to all members, yielded a total of 529 responses, 395 (74.7%) of which came from clinicians with experience with PSMD. RESULTS: Parkinsonism (68%), hemiballismus/hemichorea (61%), tremor (58%), and dystonia (54%) were by far the most commonly endorsed presentation of PSMD, although this varied by region. Basal ganglia stroke (76% of responders), symptoms contralateral to stroke (75%), and a temporal relationship (59%) were considered important factors for the diagnosis of PSMD. Oral medication use depended on the phenomenology of the PSMD. Almost 50% of respondents considered deep brain stimulation and ablative surgeries as options for treatment. The lack of guidelines for the diagnosis and treatment was considered the most important gap to address. CONCLUSIONS: Regionally varying opinions and practices on PSMD highlight gaps in (and mistranslation of) epidemiologic and therapeutic knowledge. Multicenter registries and prospective community-based studies are needed for the creation of evidence-based guidelines to inform the diagnosis and treatment of patients with PSMD.