Distinct patterns of functional brain connectivity correlate with objective performance and subjective beliefs.

The degree of correspondence between objective performance and subjective beliefs varies widely across individuals. Here we demonstrate that functional brain network connectivity measured before exposure to a perceptual decision task covaries with individual objective (type-I performance) and subjective (type-II performance) accuracy. Increases in connectivity with type-II performance were observed in networks measured while participants directed attention inward (focus on respiration), but not in networks measured during states of neutral (resting state) or exogenous attention. Measures of type-I performance were less sensitive to the subjects' specific attentional states from which the networks were derived. These results suggest the existence of functional brain networks indexing objective performance and accuracy of subjective beliefs distinctively expressed in a set of stable mental states.

[Moderate control of hyperglycemia after acute stroke in the intensive care unit]. / Control moderado de hiperglucemia luego de infarto cerebral agudo en la unidad de cuidados intensivos.

Hyperglycemia following an ischemic stroke has been associated with poor clinical outcome. We retrospectively assessed the effect of moderately controlled plasma glucose (correction from 135mg/dl) compared to conservative treatment (correction from 200 mg/dl), as regards neurological evolution, duration of hospitalization, at discharge and at 30 days post-discharge, also complications associated with the treatment in patients admitted to the intensive care unit. We studied 208 patients, 103 (24% diabetics) with moderate therapy and 105 (23% diabetics) with conservative treatment. The average blood glucose during hospitalization tended to be lower with the moderate treatment with no statistic significance (129 ± 30 vs. 138 ± 31 mg/dl; p = 0.06). The difference was significant in non-diabetics (119 ± 24 vs. 128 ± 24 mg/dl; p < 0.05), being even more pronounced in those non-diabetics with moderate to severe neurological deficit on admission (116 ± 23 vs. 130 ± 23 mg/dl; p < 0.01). Patients admitted with moderate to severe neurological deficit and treated with moderate regime had a better outcome at discharge and at 30 days (NIHSS variation: high 2.1 ± 2.6 vs. 3.4 ± 3; 30 days: 3.2 ± 3 vs. 4.8 ± 3; p < 0.01). The duration of hospitalization was lower in the moderate treatment group (5.7 vs. 9.2 days, p < 0.05), with no significant difference showing in the incidence of hypoglycemia in either group. In conclusion, moderate control of blood glucose in ACVi patients relates to an improved neurological outcome in those admitted with moderate to severe neurological deficits (NIH scale = 4), with a reduced hospital stay, and no substantial increase of hypoglycemia episodes.

Alerting network dysfunction in early multiple sclerosis.

The objective of this study is to assess attention in recently diagnosed relapsing-remitting multiple sclerosis patients. Twenty-seven patients with early multiple sclerosis and low clinical disability scores (EDSS<2) and 27 sex-, age-, and education-matched healthy controls underwent attention assessment using the Attentional Network Test, a computerized task designed to measure efficiency independently in 3 attentional networks (Alerting, Orienting and Executive Control). MS patients had significantly less efficiency in the Alerting network (p = .006). In contrast, in the Orienting and Executive Control networks, they did not differ from controls. A significant interaction between Alerting and Executive Control was also found in the MS patients (p = .007). Early relapsing-remitting multiple sclerosis particularly affects the Alerting domain of attention, whereas the Orienting and Executive Control domains are not affected.

Early motor predictors of recovery in patients with severe traumatic brain injury.

RESEARCH DESIGN: Retrospective observational study. OBJECTIVE: To compare motor variables between patients with severe traumatic brain injury who emerge and patients who do not emerge from vegetative state, in an attempt to identify early motor manifestations associated with consistent patient improvement. METHODS AND PROCEDURES: Patients were divided into two groups: group 1, patients who emerged from vegetative state attaining at least a state of functional interactive communication and/or functional use of two different objects (n = 8); and group 2, patients who did not emerge (n = 7). Twenty-one motor variables were compared weekly between groups until the end of the treatment programme. RESULTS: Significant differences were observed in head control (p = 0.051) and head turning (p = 0.002) variables, as well as in visual fixation and pursuit (p = 0.051) after a median of 41 days of therapy; and in head control and head turning; visual fixation and pursuit; phonation; pain localization, reach and grasp, and trunk movement (p ≤ 0.051) after a median of 212 days of programme duration. CONCLUSIONS: Head turning, together with or immediately followed by visual pursuit and fixation, proved to be clinically significant variables associated with recovery from vegetative state to higher states of consciousness beyond minimally conscious state.

The impact of bilateral cerebellar damage on theory of mind, empathy and decision making.

The extensive infarction affecting the posterior vermis and the medial and posterior regions of both cerebellar hemispheres, as well as the small central pontine lesion, seems to have disrupted multiple cerebral and brainstem cerebellar loops. These loops process information related to many cognitive domains, behavior and emotion, including decision making, empathy and theory of mind.

Higher autonomic activation predicts better performance in iowa gambling task.

OBJECTIVE: To evaluate the relationship between the autonomic nervous system basal state and performance in decision-making tasks. BACKGROUND: The link between performance in decision-making tasks and acute changes in autonomic parameters during their execution has been extensively investigated. However, there is lacking evidence regarding the relationship between decision making and basal autonomic state. METHODS: Resting autonomic nervous system activity in 18 healthy individuals was assessed by means of heart rate variability (HRV) analysis before conducting 3 different decision-making tasks: an ambiguous one, the Iowa Gambling Task; a test that assesses risk-taking behavior, the Game of Dice Task; and a test that assesses reversal learning behavior, the Reversal Learning Task. The tasks were administered in a random manner. RESULTS: There was a direct correlation between the Iowa Gambling Task net score and the resting low frequency HRV (r = 0.73; P < 0.001), which is strongly influenced by sympathetic activity. No correlations were found between HRV and the Game of Dice Task net score or the Reversal Learning Task last error trial. CONCLUSIONS: The results are compatible with the idea that a higher basal activation of autonomic nervous system is beneficial for subsequent decision-making process.

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.

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.

Globus pallidus internus firing rate modification after motor-imagination in three Parkinson's disease patients.

Motor imagery is thought to involve the same processes of movement preparation as actual movement. Imagination of a simple repetitive movement significantly decreased the firing rate of extracellular micro recording at sensorimotor neurons of globus pallidus internus in three patients with Parkinson's disease, who underwent microelectrode-guided posteroventral pallidotomy. These findings suggest, in agreement with previous clinical and functional neuroimaging studies that the motor corticostriatal circuit could be engaged in mental simulation.

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.

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.

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.

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.

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.

[Stunned myocardium after acute ischemic stroke]. / Atontamiento miocárdico luego del accidente cerebrovascular isquémico.

The so-called stunned myocardium, defined as transitory myocardial contractile dysfunction, has been clearly demonstrated in diverse clinical situations. However, stunned myocardium related to ischemic stroke has been poorly identified. We describe two patients with diagnosis of acute ischemic stroke who developed eletrocardiographic changes, cardiac enzyme increasing levels and myocardial dysfunction secondary to abnormal cardiac wall motion. At the same time the patients developed acute lung injury with rapid resolution, perhaps as a consequence of neurocardiogenic components.

Modulation of the default-mode network and the attentional network by self-referential processes in patients with disorder of consciousness.

Disorders of consciousness (DOC) are related to an altered capacity of the brain to successfully integrate and segregate information. Alterations in brain functional networks structure have been found in fMRI studies, which could account for the incapability of the brain to efficiently manage internally and externally generated information. Here we assess the modulation of neural activity in areas of the networks related to active introspective or extrospective processing in 9 patients with DOC and 17 controls using fMRI. In addition, we assess the functional connectivity between those areas in resting state. Patients were experimentally studied in an early phase after the event of brain injury (3±1 months after the event) and subsequently in a second session 4±1 months after the first session. The results showed that the concerted modulation of the default mode network (DMN) and attentional network (AN) in response to the active involvement in the task improved with the level of consciousness, reflecting an integral recovery of the brain in its ability to be engaged in cognitive processes. In addition, functional connectivity decreased between the DMN and AN with recovery. Our results help to further understand the neural underpins of the disorders of consciousness.

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.

Short apraxia screening test.

BACKGROUND: Limb apraxia comprises many different and common disorders, which are largely unrecognized essentially because there is no easy-to-use screening test sensitive enough to identify all types of limb praxis deficits. METHOD: We evaluated 70 right-handed patients with limb apraxia due to a single focal lesion of the left hemisphere and 40 normal controls, using a new apraxia screening test. The test covered 12 items including: intransitive gestures, transitive gestures elicited under verbal, visual, and tactile modalities, imitation of meaningful and meaningless postures and movements, and a multiple object test. RESULTS: Interrater reliability was maximum for a cutoff of >2 positive items identifying apraxia on the short battery (Cohen's kappa .918, p < .0001), and somewhat less for >3 items (Cohen's kappa .768, p < .0001). Although both results were statistically significant, >2 was higher, indicating greater apraxia diagnosis agreement between raters at this cutoff value. CONCLUSIONS: The screening test proved to have high specificity and sensitivity to diagnose every type of upper limb praxis deficit, thus showing advantages over previously published tests.