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.

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.

Decision-making impairment in patients with multiple sclerosis: a case-control study.

OBJECTIVES: To assess decision-making under explicit risk conditions in relapsing-remitting multiple sclerosis patients and its relationship to decisions made under conditions of ambiguity. To assess cognitive functions related to decision-making performance in patients with multiple sclerosis (MS). SETTING: MS center in Buenos Aires, Argentina. PARTICIPANTS: 27 patients with relapsing-remitting multiple sclerosis and 27 sex-matched, age-matched and education-matched healthy controls. INTERVENTION: Neuropsychological assessment and decision-making evaluation using the Game of Dice Task and the Iowa Gambling Task. OUTCOMES: Game of Dice Task and the Iowa Gambling Task scores. RESULTS: Patients with MS showed significantly poorer performance on the Game of Dice Task, choosing disadvantageous dice more often (p=0.019), as well as significantly lower overall scores in the Iowa Gambling Task (p=0.007). Block analysis showed that patients with MS and controls had scores that were comparable for blocks 1 and 2 (p=0.15 and p=0.24, respectively). Conversely, patients with MS scored poorly on blocks 4 (p=0.003) and 5 (p=0.023), the last two of the test, corresponding to decision-making under conditions of risk. Finally, the Game of Dice Task performance together with the last three blocks of the Iowa Gambling Task were correlated with visuospatial learning, processing speed and working memory but not with executive functioning. CONCLUSIONS: Patients with MS showed deficits in decision-making under risk conditions, which might be related to deficits in visuospatial learning, processing speed and working memory.

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.

[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.

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

La hiperglucemia después de un accidente cerebrovascular isquémico (ACVi) se asocia con peor pronóstico. Se compararon retrospectivamente los efectos entre el control de la glucemia moderado (corrección a partir de 135 mg/dl) y el conservador (a partir de 200 mg/dl) en evolución neurológica, tiempo de internación y complicaciones asociadas al tratamiento de pacientes con ACVi internados en unidad de cuidados intensivos, al alta y 30 días post-egreso. Se estudiaron 208 pacientes, 103 (24% diabéticos) con tratamiento moderado y 105 (23% diabéticos) con tratamiento conservador. La glucemia media a lo largo de la internación tendió a ser menor con el tratamiento moderado sin significancia estadística (129 ± 30 vs. 138 ± 31 mg/dl; p = 0.06). La diferencia fue significativa en los no diabéticos (119 ± 24 vs. 128 ± 24 mg/dl; p < 0.05), siendo más pronunciada en aquellos no diabéticos con déficit neurológico moderado a grave al ingreso (116 ± 23 vs. 130 ± 23 mg/dl; p < 0.01). Los pacientes que ingresaron con déficit neurológico moderado a grave tuvieron mejor evolución al alta y a 30 días bajo tratamiento moderado (variación de NIHSS: alta 2.1 ± 2.6 vs. 3.4 ± 3; 30 días: 3.2 ± 3 vs. 4.8 ± 3; p < 0.01). La duración de la internación fue menor con tratamiento moderado (6 ± 5 vs. 9 ± 5 días; p < 0.05). No hubo diferencias significativas en la incidencia de hipoglucemias. En conclusión, el control moderado de la glucemia en pacientes con ACVi se asoció con mejor evolución neurológica en aquellos que ingresaban con déficit neurológico moderado a grave (escala de NIH = 4), y una hospitalización más corta, sin un aumento sustancial de episodios de hipoglucemia.

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.

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

La hiperglucemia después de un accidente cerebrovascular isquémico (ACVi) se asocia con peor pronóstico. Se compararon retrospectivamente los efectos entre el control de la glucemia moderado (corrección a partir de 135 mg/dl) y el conservador (a partir de 200 mg/dl) en evolución neurológica, tiempo de internación y complicaciones asociadas al tratamiento de pacientes con ACVi internados en unidad de cuidados intensivos, al alta y 30 días post-egreso. Se estudiaron 208 pacientes, 103 (24% diabéticos) con tratamiento moderado y 105 (23% diabéticos) con tratamiento conservador. La glucemia media a lo largo de la internación tendió a ser menor con el tratamiento moderado sin significancia estadística (129 ± 30 vs. 138 ± 31 mg/dl; p = 0.06). La diferencia fue significativa en los no diabéticos (119 ± 24 vs. 128 ± 24 mg/dl; p < 0.05), siendo más pronunciada en aquellos no diabéticos con déficit neurológico moderado a grave al ingreso (116 ± 23 vs. 130 ± 23 mg/dl; p < 0.01). Los pacientes que ingresaron con déficit neurológico moderado a grave tuvieron mejor evolución al alta y a 30 días bajo tratamiento moderado (variación de NIHSS: alta 2.1 ± 2.6 vs. 3.4 ± 3; 30 días: 3.2 ± 3 vs. 4.8 ± 3; p < 0.01). La duración de la internación fue menor con tratamiento moderado (6 ± 5 vs. 9 ± 5 días; p < 0.05). No hubo diferencias significativas en la incidencia de hipoglucemias. En conclusión, el control moderado de la glucemia en pacientes con ACVi se asoció con mejor evolución neurológica en aquellos que ingresaban con déficit neurológico moderado a grave (escala de NIH = 4), y una hospitalización más corta, sin un aumento sustancial de episodios de hipoglucemia.(AU)

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.(AU)

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

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.

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.

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.

State-dependent changes of connectivity patterns and functional brain network topology in autism spectrum disorder.

Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that functional connectivity changes in opposite ways in ASD and typicals as attention shifts from external world towards one's body generated information. Furthermore, ASD subject alter more markedly than typicals their connectivity across cognitive states. Using differences in brain connectivity across conditions, we ranked brain regions according to their classification power. Anterior insula and dorsal-anterior cingulate cortex were the regions that better characterize ASD differences with typical subjects across conditions, and this effect was modulated by ASD severity. These results pave the path for diagnosis of mental pathologies based on functional brain networks obtained from a library of mental states.

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 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.

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.

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.