Cecile Gallea

The involuntary nature of conversion disorder

Background: What makes a movement feel voluntary, and what might make it feel involuntary? Motor conversion disorders are characterized by movement symptoms without a neurologic cause. Conversion movements use normal voluntary motor pathways, but the symptoms are paradoxically experienced as involuntary, or lacking in self-agency. Self-agency is the experience that one is the cause of ones own actions. The matched comparison between the prediction of the action consequences (feed-forward signal) and actual sensory feedback is believed to give rise to self-agency and has been in part associated with the right inferior parietal cortex. Using fMRI, we assessed the correlates of self-agency during conversion tremor. Methods: We used a within-subject fMRI block design to compare brain activity during conversion tremor and during voluntary mimicked tremor in 8 patients. Results: The random effects group analysis showed that conversion tremor compared with voluntary tremor had right temporoparietal junction (TPJ) hypoactivity (p < 0.05 family-wise error whole brain corrected) and lower functional connectivity between the right TPJ, sensorimotor regions (sensorimotor cortices and cerebellar vermis), and limbic regions (ventral anterior cingulate and right ventral striatum). Conclusions: The right TPJ has been implicated as a general comparator of internal predictions with actual events. We propose that the right TPJ hypoactivity and lower TPJ and sensorimotor cortex interactions may reflect the lack of an appropriate sensory prediction signal. The lack of a match for the proprioceptive feedback would lead to the perception that the conversion movement is not self-generated.

Impulsive choice and response in dopamine agonist-related impulse control behaviors

RationaleDopaminergic medication-related impulse control disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson’s disease (PD).HypothesisWe hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice or greater discounting of delayed rewards in PD patients with ICDs (PDI).MethodsFourteen PDI patients, 14 PD controls without ICDs, and 16 medication-free matched normal controls were tested on the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, spatial working memory, and attentional set shifting. The EDT was used to assess choice impulsivity (hyperbolic K value), reaction time (RT), and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA.ResultsOn the EDT, there was a group by medication interaction effect [F(1,26) = 5.62; p = 0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p = 0.02) but not in PD controls (p = 0.37). PDI patients also had faster RT compared to PD controls [F(1,26) = 7.51, p = 0.01]. DA status was associated with shorter RT [F(3,24) = 8.39, p = 0.001] and decision conflict RT [F(1,26) = 6.16, p = 0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t = 2.13, df = 26, p = 0.04).ConclusionGreater impulsive choice, faster RT, faster decision conflict RT, and executive dysfunction may contribute to ICDs in PD.

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self‐monitoring, limbic processing or top‐down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2‐button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age‐ and gender‐matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top‐down regulation.

The Neural Processes Underlying Self-Agency

Self-agency (SA) is the individuals perception that an action is the consequence of his/her own intention. The neural networks underlying SA are not well understood. We carried out a novel, ecologically valid, virtual-reality experiment using blood oxygen level-dependent functional magnetic resonance imaging (fMRI) where SA could be modulated in real-time while subjects performed voluntary finger movements. Behavioral testing was also performed to assess the explicit judgment of SA. Twenty healthy volunteers completed the experiment. Results of the behavioral testing demonstrated paradigm validity along with the identification of a bias that led subjects to over- or underestimate the amount of control they had. The fMRI experiment identified 2 discrete networks. These leading and lagging networks likely represent a spatial and temporal flow of information, with the leading network serving the role of mismatch detection and the lagging network receiving this information and mediating its elevation to conscious awareness, giving rise to SA.

Magnetic resonance imaging of the substantia nigra in Parkinson's disease.

Until recently, conventional magnetic resonance imaging (MRI) was most often negative in Parkinsons disease or showed nonspecific findings. Recent developments in structural MRI, including relaxometry, magnetization transfer, and neuromelanin imaging, have demonstrated improved contrast and enabled more accurate visualization of deep brain nuclei, in particular, the substantia nigra. Meanwhile, diffusion imaging has provided useful biomarkers of substantia nigra degeneration, showing reduced anisotropy and anatomical connectivity with the striatum and thalamus. These advances in structural imaging are complemented by findings of magnetic resonance spectroscopy on brain metabolism and resting‐state functional MRI on functional connectivity. This article presents an overview of these new structural, metabolic, and resting‐state functional MRI techniques and their implications for Parkinsons disease. The techniques are reviewed in the context of their potential for better understanding the disease in terms of diagnosis and pathophysiology and as biomarkers of its progression.

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

AbstractA role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia. The following topics are discussed:The relationships between neuronal/network dysfunctions and motor abnormalities in rodent models of dystonia.Data about brain structure, cerebellar metabolism, cerebellar connections, and noninvasive cerebellar stimulation that support (or not) a role for the cerebellum in human dystonia.Connections between the cerebellum and motor cortical and sub-cortical structures that could support a role for the cerebellum in dystonia. Overall points of consensus include:Neuronal dysfunction originating in the cerebellum can drive dystonic movements in rodent model systems.Imaging and neurophysiological studies in humans suggest that the cerebellum plays a role in the pathophysiology of dystonia, but do not provide conclusive evidence that the cerebellum is the primary or sole neuroanatomical site of origin.

Individuated finger control in focal hand dystonia: An fMRI study

OBJECTIVES To better understand deficient selective motor control in focal hand dystonia by determining changes in striatal activation and connectivity in patients performing individuated finger control. METHODS Functional imaging with a 3-Tesla magnetic resonance scanner was performed on 18 patients and 17 controls during non-symptom producing tasks requiring right-handed individuated or coupled finger control. A global linear model and psychophysiologic interaction model compared individuated to coupled tasks for patients and controls separately, and the results were submitted to a group analysis. The sensorimotor (posterior) and associative (anterior) parts of the putamen were considered as seed regions for the connectivity analysis. RESULTS Compared to controls, patients had significant differences in activations and connectivity during individuated compared to coupled tasks: (i) decreased activations in the bilateral postcentral gyri, right associative posterior parietal areas, right cerebellum and left posterior putamen, while activations in the left anterior putamen were not different; (ii) increased connectivity of the left posterior putamen with the left cerebellum and left sensorimotor cortex; and (iii) increased connectivity of the left anterior putamen with bilateral supplementary motor areas, the left premotor cortex, and left cerebellum. INTERPRETATION Decreased activations in the sensorimotor putamen and cerebellum controlling the affected hand might underlie low levels of surround inhibition during individuated tasks. For identical motor performance in both groups, increased connectivity of sensorimotor and associative striato-cortical circuits in FHD suggests that both affected and unaffected territories of the striatum participate in compensatory processes.

Psychiatric Symptoms Associated with Focal Hand Dystonia

Myoclonus dystonia and idiopathic dystonia are associated with a greater frequency of obsessive compulsive disorder (OCD) and major depression. We investigated the frequency of OCD in 39 patients with primary focal hand dystonia (FHD) using a semistructured interview. OCD and subsyndromal OCD was diagnosed in 5 of 39 (12.82%) patients with FHD, whereas OCD occurs in 2.3% of the general population. Recurrent depression occurred in (7 of 39) 17.95% of patients with FHD along with a family history of depression in (16 of 39) 41.02%. Overlapping mechanisms manifesting as FHD may also predispose to OC symptoms and likely implicates a common striatal dysfunction.

Brain dynamic neurochemical changes in dystonic patients: a magnetic resonance spectroscopy study.

Measurements of the concentrations of γ‐aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single‐voxel 1H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single‐voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N‐acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5‐Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N‐acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation‐induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.

Functional Anatomy of Writing with the Dominant Hand

While writing performed by any body part is similar in style, indicating a common program, writing with the dominant hand is particularly skilled. We hypothesized that this skill utilizes a special motor network supplementing the motor equivalence areas. Using functional magnetic resonance imaging in 13 normal subjects, we studied nine conditions: writing, zigzagging and tapping, each with the right hand, left hand and right foot. We identified brain regions activated with the right (dominant) hand writing task, exceeding the activation common to right-hand use and the writing program, both identified without right-hand writing itself. Right-hand writing significantly differed from the other tasks. First, we observed stronger activations in the left dorsal prefrontal cortex, left intraparietal sulcus and right cerebellum. Second, the left anterior putamen was required to initiate all the tested tasks, but only showed sustained activation during the right-hand writing condition. Lastly, an exploratory analysis showed clusters in the left ventral premotor cortex and inferior and superior parietal cortices were only significantly active for right-hand writing. The increased activation with right-hand writing cannot be ascribed to increased effort, since this is a well-practiced task much easier to perform than some of the other tasks studied. Because parietal-premotor connections code for particular skills, it would seem that the parietal and premotor regions, together with basal ganglia-sustained activation likely underlie the special skill of handwriting with the dominant hand.