Abnormalities of motor imagery associated with somatic passivity phenomena in schizophrenia

Some patients with schizophrenia report that their limbs are under the control of an alien force (motor passivity). This is hypothesised to be due to the dysfunction of an internal self-monitoring system that normally permits distinctions between internally generated and external influences on intentional behaviour. Motor imagery is the mental simulation of specific motor actions and it is based upon the internal representation of intended but unexecuted motor actions. Therefore, the generation of motor imagery should be impaired in schizophrenia characterised by passivity phenomena. The generation of motor imagery was compared using the visually guided pointing task (VGPT) and the Florida praxis imagery questionnaire (FPIQ) between patients with schizophrenia characterised by high levels of passivity symptoms (passivity) and patients without passivity symptoms (no-passivity). In both the passivity and no-passivity groups, the speed of real motor sequences on the VGPT was constrained by the distance of the movement and the width of the target in accordance with Fitts' law. For the no-passivity group, the same relationship was found for imagined movements. However, in the passivity group, imagined movements were not constrained by Fitts' law. The effect of a 2-kg load to the limb performing real or imagined movements on the VGPT was identical in both groups. The duration of imagined movements was slowed although the duration of real movements was unaffected. The FPIQ showed that the passivity group had difficulty answering questions that required them to imagine kinaesthetic aspects of performing simple gestures. These results suggest that passivity phenomena in schizophrenia are associated with a specific inability to represent the timing of motor actions internally. This is consistent with the hypothesis that patients with passivity phenomena have difficulty with maintaining an internal representation of intentional behaviour.     

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia

BACKGROUND: Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study two cortically activated inhibitory neuronal mechanisms that suppress ongoing tonic voluntary electromyographic activity in contralateral (postexcitatory inhibition [PI]) and ipsilateral (transcallosal inhibition [TI]) hand muscles. The PI follows the corticospinally mediated excitatory motor response (MEP) and is influenced by dopaminergic neurotransmission. TI reflects transcallosally mediated inhibition of the contralateral motor cortex, leading to motor inhibition in muscles ipsilateral to stimulation. PI and TI were studied to explore whether dopaminergic neurotransmission or interhemispheric transfers are altered in schizophrenia. METHODS: TMS was performed in 16 patients with this disease and in 16 healthy control subjects. Surface electromyographic activity was recorded bilaterally from the first dorsal interosseous muscle during a sustained strong isometric contraction. RESULTS: When compared with the findings in healthy subjects, patients with schizophrenia had a significantly longer PI and TI. The changes of the PI support the notion of an overactivity of the central dopaminergic system in schizophrenia. CONCLUSION: The prolonged TI suggests an abnormal activation of interhemispheric connections between the motor cortices and may be related to previously reported pathology of the corpus callosum in schizophrenic patients.     

Abnormalities of cingulate gyrus neuroanatomy in schizophrenia

OBJECTIVE AND METHODS: Abnormalities of the neuroanatomy of the gray matter of the cingulate gyrus, especially its anterior segment, have been suggested to be an important characteristic of schizophrenia. In this study, T1-weighted magnetic resonance scans were collected in 53 individuals with schizophrenia and 68 comparison subjects matched for age, gender, race and parental socioeconomic status. We applied Labeled Cortical Mantle Distance Mapping to assess the volume, surface area and thickness of the cortical mantle within the anterior (AC) and posterior (PC) segments of the cingulate gyrus, excluding the paracingulate gyrus, and related these anatomical measures to measures of psychopathology and illness duration. RESULTS: After covarying for total cerebral volume, individuals with schizophrenia showed smaller AC gray matter volume (p=0.024), thickness (trend, p=0.081), but not surface area (p=0.16), than comparison subjects. Similar group differences were found for PC gray matter volume (p=0.0005) and thickness (trend, p=0.055), but not surface area (p=0.15). Across both groups, there was a significant L>R asymmetry in thickness of the AC, and a significant L>R asymmetry in the surface area of the PC. However, there were no significant group-by-hemisphere interactions. In the individuals with schizophrenia, thinning of the AC, but not the PC, was correlated with a longer duration of illness and a greater severity of psychotic symptoms. CONCLUSIONS: Individuals with schizophrenia showed smaller gray matter volumes across the entire cingulate gyrus, mostly due to a reduction in cortical mantle thickness. However, structural measures of the AC were more closely related to clinical features of the illness.     

Abnormalities of cerebral lateralization in schizophrenia patients

Initial lateral eye movements (LEMs) have been shown to be associated with activation of the contralateral frontal lobes. Using LEM as a criterion measure of activation, schizophrenics were compared to normals with respect to the processing of four types of stimuli: verbal nonemotional (VNE), verbal emotional (VE), spatial nonemotional (SNE), and spatial emotional (SE). Our results indicate that schizophrenics initiate thought in their left hemisphere significantly more often than controls when one compares all test conditions and on VNE, VE, and SE material. Neither medication nor level of education had an appreciable effect on LEM in either group. However, sex was a significant variable; women irrespective of diagnosis consistently used the left hemisphere more often than men. The inappropriate initiation of thought on SE material as well as the overall increase in left hemisphere activity suggest left hemisphere disorder. This is consistent with other findings that suggest a left hemisphere locus of disturbance in schizophrenia.     

Abnormalities of the septum pellucidum in schizophrenia

The authors present two cases of schizophrenia in young males who have malformations of the septum pellucidum, a thin sheet of cells and fibers located in the midline of the brain that separates the lateral ventricles. These cases are discussed in the context of newly proposed neurodevelopmental models of schizophrenia.     

Abnormalities of motor timing in Huntington's disease

The ability of patients with Huntington's disease (HD) and control subjects to produce rhythmic finger tapping movements at target frequencies (1-5 Hz) signalled by auditory cues, and to sustain the tapping tempo following sudden withdrawal of cues, was investigated. HD performance, in both the presence and absence of cues, was characterised by, (i) marked irregularity of instantaneous tapping rates and (ii) a tendency to tap too slowly at higher (3-5 Hz) frequency targets and too rapidly at low target frequencies. Analysis of the variability of inter-tap intervals, during uncued tapping at a target rate of 1.8 Hz, using Wing and Kristofferson's model of motor timing (Wing AM, Kristofferson AB. Percept. Psychophys. 1973; 14: 5-12), indicated disturbances of both hypothetical 'clock' and 'motor implementation' systems in HD.     

Abnormalities in motor physiology in bipolar disorder

The primary purpose of this study was to examine motor physiology disturbances in a group of patients with bipolar disorder by using sensitive instrumental procedures. The secondary aim of the study was to examine the effects of the affective state on motor functions. The authors studied 67 individuals meeting DSM-IV criteria for bipolar disorder and 47 healthy comparison subjects. Electromechanical measures of force steadiness and scaling of movement velocity to distance were performed. The authors found that performance on the force steadiness and velocity scaling measures was significantly poorer in the subjects with bipolar disorder, with 58% and 63% of the patients scoring outside the normal range on the force steadiness and velocity scaling measures, respectively. Eighty-four percent of subjects showed impairment on either measure, and 37% showed impairment on both measures. The force steadiness and velocity scaling abnormalities appeared to occur independently of one another and also were not associated with affective state or current medication status. This study demonstrates that motor abnormalities suggestive of basal ganglia dysfunction occur in many patients with bipolar disorder.     

Abnormalities of thalamic volume and shape in schizophrenia

OBJECTIVE: Postmortem and neuroimaging studies of schizophrenia have reported deficits in the volume of the thalamus and its component nuclei. However, the pattern of shape change associated with such volume loss has not been investigated. In this study, alterations in thalamic volume, shape, and symmetry were compared in subjects with and without schizophrenia. METHOD: T(1)-weighted magnetic resonance scans were collected in 52 schizophrenia and 65 comparison subjects matched for age, gender, race, and parental socioeconomic status. High-dimensional (large-deformation) brain mapping was used to assess thalamic morphology. RESULTS: Significant differences in thalamic volume, deformities of thalamic shape at the anterior and posterior extremes of the structure, and a significant exaggeration of thalamic asymmetry (i.e., left smaller than right) were found in the schizophrenia subjects. After covarying for total cerebral volume, the difference in thalamic volume became insignificant. When information about thalamic shape was combined with previously collected information about hippocampal shape, the discrimination between schizophrenia patients and comparison subjects was improved. CONCLUSIONS: Thalamic volume was smaller than normal in schizophrenia patients, but only proportionate to reductions in reduced total cerebral volume. The presence of changes in thalamic shape and asymmetry suggest greater pathologic involvement of individual nuclei at its anterior and posterior extremes of the thalamic complex.     

Abnormalities of thalamic activation and cognition in schizophrenia

OBJECTIVE: Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. METHOD: Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. RESULTS: Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. CONCLUSIONS: These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.     

Quantitative analyses of voluntary orofacial motor control in schizophrenia and tardive dyskinesia

This paper reports the results of an investigation of voluntary control of lip, jaw, and tongue movements in schizophrenic patients with and without tardive dyskinesia. The aims of the study were to determine if voluntary orofacial motor control is disrupted in schizophrenia and to evaluate the relationship between voluntary motor control deficits and selected neurological and behavioral variables. Twenty-two schizophrenic patients and 13 normal control subjects were studied. Of the patients, 11 had moderate to severe TD. Analyses were made of performance on pursuit tracking tasks to evaluate differences between TD and non-TD patients and between medicated and currently unmedicated patients. The results indicated significant group differences in voluntary orofacial motor control. The finding that many non-TD patients exhibited voluntary motor dyscontrol suggests that this may represent a disorder independent of the involuntary dyskinesia. The findings indicated that the level of neuroleptic and/or antiparkinsonian medication was unrelated to the degree of voluntary motor control impairment. The results are discussed in terms of probable neurophysiological mechanisms underlying the motor control deficits in schizophrenia.     

Abnormalities of central motor conduction in Parkinson''s disease

The new technique of magnetic stimulation was used to measure amplitude of the motor evoked potential (MEP) recorded from abductor digiti minimi whilst stimulating at the head, and motor conduction time (MCT) between head and neck. Bilateral studies were made in 12 normal subjects and 56 patients with Parkinson's disease. The amplitudes of the MEPs were were significantly larger (P < 0.05) in the patients (mean 1.6 mV, SD 1.4) compared with the normal subjects (mean 0.9 mV, SE 0.6). MCTs were significantly shorter (P < 0.001) in patients (mean 8.1 ms, SD 1.3) compared with the normal subjects (mean 9.4 ms, SD 1.2). Although the pathophysiological basis of these changes has not been determined, they provide objective measurements which may be clinically valuable in monitoring therapy.     

Smooth-pursuit eye-movement dysfunction and motor control in schizophrenia: A follow-up study

Smooth-pursuit eye-tracking data of 63 schizophrenic patients and 52 normal controls are presented and compared with data collected on the same subjects 2 years earlier. Despite considerable clinical stabilization of the patients the overall eye-tracking performance did not improve. Intrasubject stability over 2 years was moderate. Eye-tracking impairment was significantly correlated with number of psychomotor soft signs and with number of errors in an antisaccade task. The correlations indicate that impairment of smooth-purisuit eye movements is likely to be a consequence of deficient motor control.This research was supported by the Bundesministerium für Forschung und Technologie, Germany     

Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia

BACKGROUND: Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the general population. Glucoregulatory abnormalities have also been associated with the use of antipsychotic medications themselves. While antipsychotics may increase adiposity, which can decrease insulin sensitivity, disease- and medication-related differences in glucose regulation might also occur independent of differences in adiposity. METHODS: Modified oral glucose tolerance tests were performed in schizophrenic patients (n = 48) receiving clozapine, olanzapine, risperidone, or typical antipsychotics, and untreated healthy control subjects (n = 31), excluding subjects with diabetes and matching groups for adiposity and age. Plasma was sampled at 0 (fasting), 15, 45, and 75 minutes after glucose load. RESULTS: Significant time x treatment group interactions were detected for plasma glucose (F(12,222) = 4.89, P<.001) and insulin (F(12,171) = 2.10, P =.02) levels, with significant effects of treatment group on plasma glucose level at all time points. Olanzapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at all time points, in comparison with patients receiving typical antipsychotics as well as untreated healthy control subjects. Clozapine-treated patients had significant (1.0-1.5 SDs) glucose elevations at fasting and 75 minutes after load, again in comparison with patients receiving typical antipsychotics and untreated control subjects. Risperidone-treated patients had elevations in fasting and postload glucose levels, but only in comparison with untreated healthy control subjects. No differences in mean plasma glucose level were detected when comparing risperidone-treated vs typical antipsychotic-treated patients and when comparing typical antipsychotic-treated patients vs untreated control subjects. CONCLUSION: Antipsychotic treatment of nondiabetic patients with schizophrenia can be associated with adverse effects on glucose regulation, which can vary in severity independent of adiposity and potentially increase long-term cardiovascular risk.     

Abnormalities in the establishment of feeling of self-agency in schizophrenia

BackgroundPeople usually feel they cause their own actions and the consequences of those actions, i.e., they attribute behavior to the proper agent. Research suggests that there are two routes to the experience of self-agency: 1) an explicit route, where one has the intention to obtain a goal (if it occurs, I must have done it) and 2) an implicit route, where information about the goal is unconsciously available and increases the feeling of self-agency. Schizophrenia patients typically experience no behavioral control and exhibit difficulties in distinguishing one's own actions from those of others. The present study investigates differences in both routes to self-agency experiences between schizophrenia patients and controls.MethodsTwenty-three schizophrenia patients and 23 controls performed a task where they performed an action (button press) and subsequently indicated whether or not they were the agent of the consequence of this action (the outcome) on a 9-point scale. The task can be manipulated to measure both the explicit and implicit route (by using priming) to the experience of self-agency.ResultsIn the explicit condition (participants intended to produce a specific outcome, and this outcome matched their goal), both groups experienced enhanced self-agency. In the implicit condition (the outcome matched the primed outcome), healthy controls showed increased self-agency over the outcome, while patients did not. Potential differences in task motivation and attention did not explain these findings.ConclusionsThese findings provide new evidence for the idea that implicit processes leading to feelings of self-agency may be disturbed in schizophrenia.     

Earlier age of first diagnosis in schizophrenia is related to impaired motor control

We examined the control of motor behavior in relation to age of first diagnosis (AFD; an approximation of age of onset) in schizophrenia. We hypothesized that earlier AFD reflects increased vulnerability to the disorder, vulnerability that may be indexed by elevated levels of motor abnormality. AFD, symptom and demographic features, motor performance on a line drawing task, and the presence and severity of dyskinesia and extrapyramidal side effects were evaluated in 65 chronic schizophrenia subjects. More severely impaired motor control was significantly related to an earlier age of diagnosis. Potential confounds, including age, gender, education, length of illness, current medication dosage, symptom status, and motor side effects, did not appear to influence this relationship, although greater chronicity appeared to be independently related to more severely impaired motor control. In summary, the data are consistent with the hypothesis that an earlier AFD is associated with more pronounced motor impairment.     

Failure of cathodal direct current stimulation to improve fine motor control in musician's dystonia

Musician's dystonia (MD) is a task‐specific movement disorder with a loss of voluntary motor control in highly trained movements. Defective inhibition on different levels of the central nervous system is involved in its pathophysiology. Cathodal transcranial direct current stimulation (ctDCS) diminishes excitability of the motor cortex and improves performance in overlearned tasks in healthy subjects. The aim of this study was to investigate whether ctDCS improves fine motor control in MD. Professional guitarists (n = 10) with MD played exercises before, directly after ctDCS, and 60 min after ctDCS. ctDCS (2 mA, 20 min) was applied on the primary motor cortex contralateral to the affected hand. Guitar exercises were video‐documented and symptoms were evaluated by three independent experts. No beneficial effect of ctDCS on fine motor control was found for the entire group. However, motor control of one guitarist improved after stimulation. This patient suffered from arm dystonia, whereas the other guitarists suffered from hand dystonia. © 2009 Movement Disorder Society