Cortico-basal Circuits Research Articles

Clinically established early Parkinson's disease patients do not show impaired use of priors in conditions of perceptual uncertainty

The ability to use past learned experiences to guide decisions is an important component of adaptive behavior, especially when decision-making is performed under time pressure or when perceptual information is unreliable. Previous studies using visual discrimination tasks have shown that this prior-informed decision-making ability is impaired in Parkinson's disease (PD), but the mechanisms underlying this deficit and the precise impact of dopaminergic denervation within cortico-basal circuits remain unclear. To shed light on this problem, we evaluated prior-informed decision-making under various conditions of perceptual uncertainty in a sample of 13 clinically established early PD patients, and compared behavioral performance with healthy control (HC) subjects matched in age, sex and education. PD patients and HC subjects performed a random dot motion task in which they had to decide the net direction (leftward vs. rightward) of a field of moving dots and communicate their choices through manual button presses. We manipulated prior knowledge by modulating the probability of occurrence of leftward vs. rightward motion stimuli between blocks of trials, and by explicitly giving these probabilities to subjects at the beginning of each block. We further manipulated stimulus discriminability by varying the proportion of dots moving coherently in the signal direction and speed-accuracy instructions. PD patients used choice probabilities to guide perceptual decisions in both speed and accuracy conditions, and their performance did not significantly differ from that of HC subjects. An additional analysis of the data with the diffusion decision model confirmed this conclusion. These results suggest that the impaired use of priors during visual discrimination observed at more advanced stages of PD is independent of dopaminergic denervation, though additional studies with larger sample sizes are needed to more firmly establish this conclusion.

Focal thalamus pathology in frontotemporal dementia: Phenotype-associated thalamic profiles

BackgroundThe clinical phenotypes of frontotemporal dementia (FTD) are defined by distinctive clinical features and associated with unique cortical atrophy patterns. Clinical manifestations in FTD however are not solely driven by cortical pathology, but stem from the selective dysfunction of corticobasal circuits, the majority of which are relayed through thalamic nuclei. The objective of this study is the systematic radiological characterisation of thalamic pathology across the clinical spectrum of FTD to describe phenotype-associated thalamic signatures. Methods170 participants were included in a multimodal, prospective neuroimaging study to evaluate thalamic degeneration at a nuclear, vertex, and morphometric level using a uniform imaging protocol and a multimodal analysis approach. ResultsPatients with behavioural variant FTD (bvFTD), non-fluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA) and amyotrophic lateral sclerosis-FTD (ALS-FTD) exhibit distinctive thalamic disease-burden profiles with the preferential degeneration of specific thalamic nuclei. While vertex analyses reveal largely overlapping thalamic atrophy patterns, morphometric analyses successfully capture focal intra-thalamic degeneration. ConclusionsMirroring selective cortical vulnerability, focal rather than global thalamic atrophy characterises the clinical subtypes of FTD. Thalamic degeneration is a likely contributor to the heterogeneity of clinical manifestations observed in FTD. As thalamic imaging techniques capture different facets of pathological change and differ in their sensitivity to detect distinguishing features, future studies should implement a multimodal approach with complementary MRI techniques.

Magnetoencephalography detects phase-amplitude coupling in Parkinson\u2019s disease

To characterize Parkinson’s disease, abnormal phase-amplitude coupling is assessed in the cortico-basal circuit using invasive recordings. It is unknown whether the same phenomenon might be found in regions other than the cortico-basal ganglia circuit. We hypothesized that using magnetoencephalography to assess phase-amplitude coupling in the whole brain can characterize Parkinson’s disease. We recorded resting-state magnetoencephalographic signals in patients with Parkinson’s disease and in healthy age- and sex-matched participants. We compared whole-brain signals from the two groups, evaluating the power spectra of 3 frequency bands (alpha, 8–12 Hz; beta, 13–25 Hz; gamma, 50–100 Hz) and the coupling between gamma amplitude and alpha or beta phases. Patients with Parkinson’s disease showed significant beta–gamma phase-amplitude coupling that was widely distributed in the sensorimotor, occipital, and temporal cortices; healthy participants showed such coupling only in parts of the somatosensory and temporal cortices. Moreover, beta- and gamma-band power differed significantly between participants in the two groups (P < 0.05). Finally, beta–gamma phase-amplitude coupling in the sensorimotor cortices correlated significantly with motor symptoms of Parkinson’s disease (P < 0.05); beta- and gamma-band power did not. We thus demonstrated that beta–gamma phase-amplitude coupling in the resting state characterizes Parkinson’s disease.

Processing of Real-World, Dynamic Natural Stimuli in Autism is Linked to Corticobasal Function.

Many individuals with autism spectrum disorder (ASD) have been shown to perceive everyday sensory information differently compared to peers without autism. Research examining these sensory differences has primarily utilized nonnatural stimuli or natural stimuli using static photos with few having utilized dynamic, real-world nonverbal stimuli. Therefore, in this study, we used functional magnetic resonance imaging to characterize brain activation of individuals with high-functioning autism when viewing and listening to a video of a real-world scene (a person bouncing a ball) and anticipating the bounce. We investigated both multisensory and unisensory processing and hypothesized that individuals with ASD would show differential activation in (a) primary auditory and visual sensory cortical and association areas, and in (b) cortical and subcortical regions where auditory and visual information is integrated (e.g. temporal-parietal junction, pulvinar, superior colliculus). Contrary to our hypotheses, the whole-brain analysis revealed similar activation between the groups in these brain regions. However, compared to controls the ASD group showed significant hypoactivation in the left intraparietal sulcus and left putamen/globus pallidus. We theorize that this hypoactivation reflected underconnectivity for mediating spatiotemporal processing of the visual biological motion stimuli with the task demands of anticipating the timing of the bounce event. The paradigm thus may have tapped into a specific left-lateralized aberrant corticobasal circuit or loop involved in initiating or inhibiting motor responses. This was consistent with a dual "when versus where" psychophysical model of corticobasal function, which may reflect core differences in sensory processing of real-world, nonverbal natural stimuli in ASD. Autism Res 2020, 13: 539-549. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: To understand how individuals with autism perceive the real-world, using magnetic resonance imaging we examined brain activation in individuals with autism while watching a video of someone bouncing a basketball. Those with autism had similar activation to controls in auditory and visual sensory brain regions, but less activation in an area that processes information about body movements and in a region involved in modulating movements. These areas are important for understanding the actions of others and developing social skills.

P23. Basal ganglia pathology in amyotrophic lateral sclerosis is associated with cognitive and behavioural changes

Introduction Extrapyramidal, cognitive, and sensory deficits are increasingly recognised in patients with amyotrophic lateral sclerosis (ALS), suggesting dysfunction of specific frontostriatal, nigrostriatal and corticobasal circuits. While significant basal ganglia involvement has been demonstrated by recent histopathology and neuroimaging studies, subcortical pathology in ALS has not been studied in relation to cognitive and behavioural deficits. Here, we evaluate basal ganglia involvement along the continuum of ALS, ALS with cognitive and behavioural deficits, and ALS with comorbid frontotemporal dementia (ALS-FTD), using multiple, complementary imaging techniques. Methods Volumetric, shape, and density analyses were performed for seven subcortical structures: thalamus, amygdala, nucleus accumbens, hippocampus, caudate nucleus, pallidum, and putamen. Patients were allocated into three study-groups: C9orf72-negative ALS patients without cognitive or behavioural impairment (“ALS-Nci”, n = 42), ALS patients with cognitive and/or behavioural impairment (“ALS-Plus”, n = 18), and ALS patients with comorbid FTD (“ALS-FTD”, n = 7), matched for disease duration and severity. An age-, gender-, and education matched group of healthy controls was also included (“HC”, n = 39). Results Volumetric analyses revealed intergroup differences for six subcortical structures when adjusting for total intracranial volume and controlling for age: caudate nucleus (p = 0.023), thalamus (p Conclusion A gradient of incremental basal ganglia pathology was observed across the ALS/ALS-FTD spectrum, suggesting that the degree of subcortical grey matter pathology in C9orf72-negative ALS is closely associated with cognitive and behavioural changes. The observed changes in shape and lesion location are indicating a disease specific degeneration of subcortical structures and suggest the disruption of frontrostriatal and corticobasal circuits in ALS.

Coupling in the cortico-basal ganglia circuit is aberrant in the ketamine model of schizophrenia

Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals׳ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1–4; theta 4–8Hz) and the amplitude of high-gamma (~80Hz) and high-frequency oscillations (HFO) (~150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO’s across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients.

Trouble obsessionnel compulsif secondaire. À propos d'un cas

The discovery by morphological cerebral imagery methods of abnormalities or lesions in patients with psychiatric diseases has led to the concept of secondary troubles. This concept is discussed from the case of a patient with a typical obsessive–compulsive disorder (OCD) in whom MRI found a left temporal arachnoid cyst, which was probably incidental, and a bilateral lesion of the globi pallidi which was the possible consequence of an old carbon monoxide intoxication. It is suggested that the distinction: primary versus secondary troubles is going to fade with the occurrence of more efficient methods of cerebral imagery. This new case of secondary OCD confirms the role of a disjunction or a dysfunction (in primary forms) of a cortico-basal circuit as a common pathophysiologic mechanism in OCD. Neurosurgical functional manipulation of this circuit represents a new hope for the therapeutics.

Altered cortical excitability in obsessive-compulsive disorder.

To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD). Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders. We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus. Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics. The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.