Lateralization of brain activity during motor planning of proximal and distal gestures.

Praxis functions are predominantly processed by the left hemisphere. However, limb apraxia is found in less than 50% of patients with left hemisphere damage, and also, although infrequently, in patients with right hemisphere damage. We studied brain representation of preparation/planning of tool-use pantomime separating the gestures involving mostly distal limb control (e.g., using scissors) from those involving proximal limb control (e.g., hammering). During the fMRI scan transitive pantomimes were performed with the dominant and the non-dominant hand by right-handed healthy subjects. Random and voxel-based analysis through laterality index (LI) calculation, demonstrated that for both limbs, distal gesture planning was in general left lateralized, while for the proximal condition the representation was found to be more bilateral particularly in the inferior frontal gyrus. LI distributions across subjects indicated that while the majority of subjects are left-hemispheric dominant for praxis, there are a minority with the opposite lateralization. Functional connectivity analysis showed that while the correlation between homolog areas involved in gesture production was high irrespective of gesture type, their correlation to the supplementary motor area was high in proximal but not distal conditions. Therefore, transitive gestures, when pantomimed to verbal commands, are differentially represented inter and intra hemispherically depending on whether the gesture is performed with the right or left arm or whether it involves predominantly distal or proximal limb movements. Furthermore, the representation of the different types of gestures may be related to a modulation of the connectivity between areas involved in motor planning.

Neural correlates of musical creativity: differences between high and low creative subjects.

Previous studies of musical creativity suggest that this process involves multi-regional intra and interhemispheric interactions, particularly in the prefrontal cortex. However, the activity of the prefrontal cortex and that of the parieto-temporal regions, seems to depend on the domains of creativity that are evaluated and the task that is performed. In the field of music, only few studies have investigated the brain process of a creative task and none of them have investigated the effect of the level of creativity on the recruit networks. In this work we used magnetic resonance imaging to explore these issues by comparing the brain activities of subjects with higher creative abilities to those with lesser abilities, while the subjects improvised on different rhythmic fragments. We evaluated the products the subjects created during the fMRI scan using two musical parameters: fluidity and flexibility, and classified the subjects according to their punctuation. We examined the relation between brain activity and creativity level. Subjects with higher abilities generated their own creations based on modifications of the original rhythm with little adhesion to it. They showed activation in prefrontal regions of both hemispheres and the right insula. Subjects with lower abilities made only partial changes to the original musical patterns. In these subjects, activation was only observed in left unimodal areas. We demonstrated that the activations of prefrontal and paralimbic areas, such as the insula, are related to creativity level, which is related to a widespread integration of networks that are mainly associated with cognitive, motivational and emotional processes.

The effect of the visual context in the recognition of symbolic gestures.

BACKGROUND: To investigate, by means of fMRI, the influence of the visual environment in the process of symbolic gesture recognition. Emblems are semiotic gestures that use movements or hand postures to symbolically encode and communicate meaning, independently of language. They often require contextual information to be correctly understood. Until now, observation of symbolic gestures was studied against a blank background where the meaning and intentionality of the gesture was not fulfilled. METHODOLOGY/PRINCIPAL FINDINGS: Normal subjects were scanned while observing short videos of an individual performing symbolic gesture with or without the corresponding visual context and the context scenes without gestures. The comparison between gestures regardless of the context demonstrated increased activity in the inferior frontal gyrus, the superior parietal cortex and the temporoparietal junction in the right hemisphere and the precuneus and posterior cingulate bilaterally, while the comparison between context and gestures alone did not recruit any of these regions. CONCLUSIONS/SIGNIFICANCE: These areas seem to be crucial for the inference of intentions in symbolic gestures observed in their natural context and represent an interrelated network formed by components of the putative human neuron mirror system as well as the mentalizing system.

Autonomic nervous system activation during social cognition tasks in patients with schizophrenia and their unaffected relatives.

OBJECTIVE: The objective of the study was to determine whether patients with schizophrenia and their unaffected first-degree relatives have abnormal autonomic nervous system (ANS) responses to social cognition tasks. BACKGROUND: Social cognition impairments are significant in schizophrenia. ANS activity has been shown to be abnormal in schizophrenia patients, and some of the abnormalities seem to be shared by patients' unaffected relatives. METHOD: Heart rate variability (HRV) was measured at rest and during social cognition tasks, in patients with schizophrenia, their nonpsychotic first-degree relatives, and matched healthy controls (n=19 in each group). RESULTS: Social cognition tasks induced a shortening of the RR interval in unaffected relatives, but not in patients. Social cognition tasks generated decreases in high-frequency (indicating cardiac vagal activity) and low-frequency (reflecting predominantly sympathetic activity) HRV in patients. In relatives, the decrease occurred in the high-frequency component only. Low-frequency HRV was higher in patients during a theory of mind task than a control task. These changes were not observed in the controls. CONCLUSIONS: Social cognitive tasks induce a pattern of peripheral autonomic activity different from that seen in generic arousal responses, and this pattern is abnormal in schizophrenia patients. Autonomic abnormalities in unaffected first-degree relatives seem restricted to the parasympathetic division of the ANS.

Asymmetrical contribution of brain structures to treatment-resistant depression as illustrated by effects of right subgenual cingulum stimulation.

Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate in men. While many patients are successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.

Continuous subcutaneous apomorphine for severe disorders of consciousness after traumatic brain injury.

BACKGROUND: The prognosis of long-term severe disorders of consciousness due to traumatic brain injury is discouraging. There is little definitive evidence of the underlying mechanisms, but a deficiency of the dopaminergic system may be involved. METHODS: In a prospective open-labelled clinical study, the feasibility, relative efficacy and safety of continuous subcutaneous (s.c.) administration of apomorphine in Vegetative State (VS) or Minimally Conscious State (MCS) patients due to severe traumatic brain injury (TBI) was tested. Apomorphine was administered to eight patients. Outcome measures were the Coma Near-Coma Scale (CNCS) and Disability Rating Scale (DRS). RESULTS: Drug management was implemented without any problems. There was improvement in the primary outcomes for all patients. Awakening was seen as rapidly as within the first 24 hours of drug administration and as late as 4 weeks. Seven of the patients had completely recovered consciousness. All improvements were sustained for at least 1 year, even after apomorphine was discontinued. Drug-related adverse events were all anticipated and resolved after the dose was reduced. CONCLUSION: Based on this open-label pilot study, continuous s.c. apomorphine infusion appears to be feasible, safe and potentially effective in improving consciousness in patients in VS and MCS due to severe TBI.

Emotion processing and theory of mind in schizophrenia patients and their unaffected first-degree relatives.

Previous studies have suggested that social cognition is affected in individuals with schizophrenia. The purpose of this study was to explore to what extent social cognition deficits are shared by unaffected first-degree relatives, and the nature of the relationship between performance in different paradigms of social cognition. 20 Schizophrenia patients (7 females, 31+/-10 years), 20 healthy age- and gender-matched individuals, 20 unaffected first-degree relatives of the schizophrenia patients (11 females, 50+/-20 years), and 20 healthy individuals matched for age and gender were recruited. Patients showed deficits in the detection of social Faux Pas (0.80+/-0.17 vs. controls: 0.94+/-0.09, p=0.025) and the correct identification of Theory of Mind stories (0.71+/-0.13 vs. controls: 0.82+/-0.12, p=0.038). Relatives performed poorly in the Faces Test (0.83+/-0.14 vs. controls: 0.9+/-0.08, p=0.048), the Reading the Mind in the Eyes Test (0.59+/-0.17 vs. controls: 0.71+/-0.14, p=0.046) and the detection of social Faux Pas (0.8+/-0.2 vs. controls: 0.93+/-0.09, p=0.024). Abnormalities were independent of age, years of education, and general cognitive performance in patients and their relatives. Performance in an Emotion Processing task (Faces Test) was correlated with performance in theory of mind tests in healthy individuals and relatives of patients with schizophrenia only. These results suggest that schizophrenia patients and their unaffected first-degree relatives display similar but nonidentical patterns of social cognition processing.

Fast awakening from minimally conscious state with apomorphine.

BACKGROUND: Traumatic brain injury (TBI) can induce long-term severe disorders of consciousness. Evidence suggests an underlying dopaminergic deficit. Dopamine agonists may therefore play an important role in recovery of consciousness. OBJECTIVE: To explore the response to continuous subcutaneous administration of apomorphine in a patient who had remained in minimally conscious state for 104 days and to evaluate the anatomical substrate of the effect. DESIGN: A prospective, open-label, daily treatment, dose-escalation single case clinical study, with retrospective diffusion tensor image (DTI) evaluation. RESULTS: On the fist day of treatment, the patient was able to move his limbs on command and answer yes/no questions which had not been the case prior to apomorphine administration. Subsequently there was a full recovery of consciousness and substantial functional recovery that was sustained even after apomorphine discontinuation. At the highest dose, mild dyskinesias were observed. These resolved with a lowering of the dose. DTI demonstrated a decrease of thalamocortical and corticothalamic projections in this MCS patient compared to normal volunteers. CONCLUSION: Although this is an open-label single-patient case report, the data are consistent with the theory that a dopaminergic deficit underlies MCS and that it may be overcome with apomorphine administration.

Heart rate variability response to mental arithmetic stress is abnormal in first-degree relatives of individuals with schizophrenia.

BACKGROUND: Schizophrenia patients exhibit an abnormal autonomic response to mental stress. We sought to determine the cardiac autonomic response to mental arithmetic stress in their unaffected first-degree relatives. METHODS: Heart rate variability (HRV) analysis was performed on recordings obtained before, during, and after a standard mental arithmetic task to induce mental stress. 22 unaffected first-degree relatives of patients meeting DSM-IV criteria for schizophrenia (R) and 22 healthy individuals (C) were included in this study. RESULTS: Patients' relatives (R) had a normal response to the mental arithmetic stress test, showing an increased heart rate compared with controls. They also displayed the characteristic pattern of relative contributions of HRV components that consists of increased low-frequency (LF) HRV and decreased high-frequency (HF) HRV. Recovery of the resting pattern of HRV immediately after stress termination was observed in healthy subjects (LF 62+/-16% vs. 74+/-10% , HF 37+/-16% vs. 25+/-10%, F=9.616, p=0.004), but not in patients' relatives (LF 60+/-19% vs. 70+/-13%, HF 40+/-19% vs. 29+/-13%, F=8.4, p=0.056). CONCLUSIONS: First-degree relatives of schizophrenia patients exhibit an abnormal pattern of protracted response to mental arithmetic stress, though less intense than that observed in patients in a previous study. This suggests that a pattern of autonomic response to stress may therefore be familial and heritable.

The neural substrate of gesture recognition.

Previous studies have linked action recognition with a particular pool of neurons located in the ventral premotor cortex, the posterior parietal cortex and the superior temporal sulcus (the mirror neuron system). However, it is still unclear if transitive and intransitive gestures share the same neural substrates during action-recognition processes. In the present study, we used event-related functional magnetic resonance imaging (fMRI) to assess the cortical areas active during recognition of pantomimed transitive actions, intransitive gestures, and meaningless control actions. Perception of all types of gestures engaged the right pre-supplementary motor area (pre-SMA), and bilaterally in the posterior superior temporal cortex, the posterior parietal cortex, occipitotemporal regions and visual cortices. Activation of the posterior superior temporal sulcus/superior temporal gyrus region was found in both hemispheres during recognition of transitive and intransitive gestures, and in the right hemisphere during the control condition; the middle temporal gyrus showed activation in the left hemisphere when subjects recognized transitive and intransitive gestures; activation of the left inferior parietal lobe and intraparietal sulcus (IPS) was mainly observed in the left hemisphere during recognition of the three conditions. The most striking finding was the greater activation of the left inferior frontal gyrus (IFG) during recognition of intransitive actions. Results show that a similar neural substrate, albeit, with a distinct engagement underlies the cognitive processing of transitive and intransitive gestures recognition. These findings suggest that selective disruptions in these circuits may lead to distinct clinical deficits.

Vertical scanning biases and their possible influence on reading direction: celtic wisdom or folly?

The reason people read from top to bottom is unknown, but could be related to brain-mediated directional biases or environmental factors. To learn if there is a brain-mediated directional bias responsible for top-down reading direction, we evaluated the directional scanning in the vertical dimension by using directional letter and face cancellation tasks. Twenty participants were instructed to cancel either target letters or faces using either an up-down or down-up direction, with the stimuli located in left, right, and center hemispace. The results indicated significant differences in completion time between the search direction (up vs. down) and spatial position for the letter cancellation task, with a faster completion time for the bottom-up scan in right space and top-down in left space. Because the left hemisphere primarily attends to contralateral right hemispace our results suggest that, when attending to letter stimuli, the left hemisphere is biased to scan in a proximal to distal (upward) direction. Although the reasons why this is reversed in left hemispace and why we did not see directional biases in the face condition remains unclear, these results do suggest that the direction in which we learn to read is inconsistent with the brain's intrinsic directional bias.

Nonlinear analysis of heart rate variability in patients with eating disorders.

Patients with anorexia nervosa or bulimia nervosa often have signs of autonomic dysfunction potentially deleterious to the heart. The aim of this study was to ascertain the nonlinear properties of heart rate variability in patients with eating disorders. A group of 33 women with eating disorders (14 anorexia, 19 bulimia) and 19 healthy controls were included in the study. Conventional time- and frequency-domain heart rate variability measurements, along with nonlinear heart rate variability measurements including the short-term fractal scaling exponent alpha and approximate entropy (ApEn) were calculated. Anorexia nervosa patients exhibited decreased values of alpha, while bulimia nervosa patients had decreased values of ApEn. Low-frequency heart rate variability was decreased in patients with anorexia. In conclusion, these results are compatible with the view that a more severe alteration of cardiac autonomic function is present in anorexia than in bulimia.

Heart rate variability response to mental arithmetic stress in patients with schizophrenia: autonomic response to stress in schizophrenia.

BACKGROUND: The vulnerability-stress hypothesis is an established model of schizophrenia symptom formation. We sought to characterise the pattern of the cardiac autonomic response to mental arithmetic stress in patients with stable schizophrenia. METHODS: We performed heart rate variability (HRV) analysis on recordings obtained before, during, and after a standard test of autonomic function involving mental stress in 25 patients with DSM-IV schizophrenia (S) and 25 healthy individuals (C). RESULTS: Patients with schizophrenia had a normal response to the mental arithmetic stress test. Relative contributions of low-frequency (LF) HRV and high-frequency (HF) HRV influences on heart rate in patients were similar to controls both at rest (LF 64+/-19% (S) vs. 56+/-16% (C); HF 36+/-19% (S) vs. 44+/-16% (C), t=1.52, p=0.136) and during mental stress, with increased LF (S: 76+/-12%, C: 74+/-11%) and decreased HF (S: 24+/-12%, C: 26+/-11%) in the latter study condition. Whilst healthy persons recovered the resting pattern of HRV immediately after stress termination (LF 60+/-15%, HF 40+/-15%, F=18.5, p<0.001), in patients HRV remained unchanged throughout the observed recovery period, with larger LF (71+/-17%) and lower HF (29+/-17%) compared with baseline (F=7.3, p=0.013). CONCLUSIONS: Patients with schizophrenia exhibit a normal response to the mental arithmetic stress test as a standard test of autonomic function but in contrast with healthy individuals, they maintain stress-related changes of cardiac autonomic function beyond stimulus cessation.

Depressive symptoms are related to decreased low-frequency heart rate variability in older adults with decompensated heart failure.

BACKGROUND/AIMS: Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. METHODS: This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients >or=65 years of age, 24-72 h after admission to the coronary care unit with a diagnosis of CHF. RESULTS: Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low-frequency HRV. CONCLUSION: These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure.

Reorganization of the human ipsilesional premotor cortex after stroke.

The substrates that mediate recovery of motor function after stroke are incompletely understood. Several primate and human studies proposed the involvement of the premotor cortex of the lesioned hemisphere. Here, we studied four chronic stroke patients with focal subcortical lesions affecting the corticospinal outflow originating in the primary motor cortex (M1) and good motor recovery. We tested the hypothesis that, in these patients, disruption of activity in the premotor cortex of the lesioned hemisphere by transcranial magnetic stimulation (TMS) would result in degraded behaviour in the paretic hand. TMS was applied to the primary motor cortex, dorsal premotor cortex (PMd) and ventral premotor cortex (PMv) of the affected (M1AH, PMdAH, PMvAH) and intact (M1IH, PMdIH, PMvIH) hemispheres of patients and healthy controls in the setting of a simple reaction time (SRT) paradigm performed with the hand contralateral to the stimulated hemisphere. TMS applied to M1 led to substantial contralateral SRT delays in both groups. TMS applied to PMdAH of patients elicited clear delays in contralateral SRT in the paretic hand, whereas TMS applied to PMdIH of patients or healthy volunteers did not. Motor evoked potentials after stimulation of PMdAH were, on average, larger and had, on average, shorter latency than after stimulation of M1AH. These results indicate that PMdAH participates as a substrate mediating functional recovery of executive motor function in patients with focal lesions of corticospinal outflow originating in M1 and good motor recovery. Our results are consistent with the hypothesis that the dorsal premotor cortex of the affected hemisphere can reorganize to control basic parameters of movement usually assigned to M1 function.

Limb-kinetic apraxia in corticobasal degeneration: clinical and kinematic features.

Current concepts regarding the organisation of the motor system indicate the existence of a frontoparietal circuit involved in prehension and manipulation, whose damage may result in a motor behavioural disorder strongly resembling the one originally described as limb-kinetic apraxia. To determine the specific clinical and kinematic features of this distinctive praxic disorder, 5 patients with corticobasal degeneration (apraxic group), 5 with Parkinson's disease (nonapraxic group), and 10 control subjects were studied by a comprehensive apraxic battery, three-dimensional motion analysis of manipulative movements and motor evoked potentials. A mathematical model [quality of movement coefficient (QMC)] was applied to quantify differential kinematic characteristics between elementary motor deficits and the praxic disorder. Transcranial magnetic stimulation was used to evaluate corticomotoneural projections and cortical inhibition. All five patients in the apraxic group exhibited a unilateral praxic deficit characterised by derangement of fractionated and segmental finger movements. QMC was significantly greater in apraxic than in nonapraxic patients (P < 0.02), revealing a chaotic movement with marked interfinger uncoordination. Conventional transcranial magnetic stimulation parameters were within normal limits in both groups of patients; however, the silent period was significantly shorter in the apraxic limb when compared with control subjects (P < 0.001). Limb-kinetic apraxia is a distinctive disorder affecting the performance of finger and hand postures and movements over and above a corticospinal or basal ganglion deficit. Disruption of the frontoparietal circuit devoted to grasping and manipulation, together with defective cortical inhibition, which would also interfere with the selection and control of hand muscle activity, are the most likely underlying physiopathological mechanisms of limb-kinetic apraxia in patients with corticobasal degeneration.