Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC).

BACKGROUND: and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue. METHODS: Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact Scale (MFIS). Pain level, anxiety severity and quality of life were secondary outcomes assessed, respectively, through the McGill Questionnaire, Hamilton Anxiety Rating Scale (HAM-A) and WHOQOL. RESULTS: Active HD-tDCS resulted in significantly greater reduction in fatigue compared to sham HD-tDCS (mean group MFIS reduction of 22.11 points vs 10.34 points). Distinct effects of HD-tDCS were observed in fatigue domains with greater effect on cognitive (mean group difference 8.29 points; effect size 1.1; 95% CI 3.56-13.01; P < .0001) and psychosocial domains (mean group difference 2.37 points; effect size 1.2; 95% CI 1.34-3.40; P < .0001), with no significant difference between the groups in the physical subscale (mean group difference 0.71 points; effect size 0.1; 95% CI 4.47-5.90; P = .09). Compared to sham, the active HD-tDCS group also had a significant reduction in anxiety (mean group difference 4.88; effect size 0.9; 95% CI 1.93-7.84; P < .0001) and improvement in quality of life (mean group difference 14.80; effect size 0.7; 95% CI 7.87-21.73; P < .0001). There was no significant difference in pain (mean group difference -0.74; no effect size; 95% CI 3.66-5.14; P = .09). CONCLUSION: An intervention with M1 targeted HD-tDCS paired with a rehabilitation program was effective in reducing fatigue and anxiety, while improving quality of life in people with PASC.

Disentangling hand and tool processing: Distal effects of neuromodulation.

Neural processing within a local brain region that responds to more than one object category (e.g., hands and tools) nonetheless have different functional connectivity patterns with other distal brain areas, which suggests that local processing can affect and/or be affected by processing in distal areas, in a category-specific way. Here we wanted to test whether administering either a hand- or tool-related training task in tandem with transcranial direct current stimulation (tDCS) to a region that responds both to hands and tools (posterior middle temporal gyrus; pMTG), modulated local and distal neural processing more for the trained than the untrained category in a subsequent fMRI task. After each combined tDCS/training session, participants viewed images of tools, hands, and animals, in an fMRI scanner. Using multivoxel pattern analysis, we found that tDCS stimulation to pMTG indeed improved the classification accuracy between tools vs. animals, but only when combined with a tool and not a hand training task. Surprisingly, tDCS stimulation to pMTG also improved classification accuracy between hands vs. animals when combined with a tool but not a hand training task. Our findings suggest that overlapping but functionally-specific networks may be engaged separately by using a category-specific training task together with tDCS - a strategy that can be applied more broadly to other cognitive domains using tDCS. By hypothesis, these effects on local processing are a direct result of within-domain connectivity constraints from domain-specific networks that are at play in the processing and organization of object representations.

Efficacy and safety of HD-tDCS and respiratory rehabilitation for critically ill patients with COVID-19 The HD-RECOVERY randomized clinical trial.

BACKGROUND AND PURPOSE: Acute Respiratory Distress Syndrome (ADRS) due to coronavirus disease 2019 (COVID-19) has been associated with muscle fatigue, corticospinal pathways dysfunction, and mortality. High-Definition transcranial Direct Current Stimulation (HD-tDCS) may be used to attenuate clinical impairment in these patients. The HD-RECOVERY randomized clinical trial was conducted to evaluate the efficacy and safety of HD-tDCS with respiratory rehabilitation in patients with moderate to severe ARDS due to COVID-19. METHODS: Fifty-six critically ill patients were randomized 1:1 to active (n = 28) or sham (n = 28) HD-tDCS (twice a day, 30-min, 3-mA) plus respiratory rehabilitation for up to 10 days or until intensive care unit discharge. The primary outcome was ventilator-free days during the first 28 days, defined as the number of days free from mechanical ventilation. Furthermore, secondary outcomes such as delirium, organ failure, hospital length of stay and adverse effects were investigated. RESULTS: Active HD-tDCS induced more ventilator-free days compared to sham HD-tDCS. Patients in the active group vs in the sham group experienced lower organ dysfunction, delirium, and length of stay rates over time. In addition, positive clinical response was higher in the active vs sham group. There was no significant difference in the prespecified secondary outcomes at 5 days. Adverse events were similar between groups. CONCLUSIONS: Among patients with COVID-19 and moderate to severe ARDS, use of active HD-tDCS compared with sham HD-tDCS plus respiratory rehabilitation resulted in a statistically significant increase in the number of ventilator-free days over 28 days. HD-tDCS combined with concurrent rehabilitation therapy is a safe, feasible, potentially add-on intervention, and further trials should examine HD-tDCS efficacy in a larger sample of patients with COVID-19 and severe hypoxemia.

Raman spectroscopy and sciatic functional index (SFI) after low-level laser therapy (LLLT) in a rat sciatic nerve crush injury model.

Axonotmesis causes sensorimotor and neurofunctional deficits, and its regeneration can occur slowly or not occur if not treated appropriately. Low-level laser therapy (LLLT) promotes nerve regeneration with the proliferation of myelinating Schwann cells to recover the myelin sheath and the production of glycoproteins for endoneurium reconstruction. This study aimed to evaluate the effects of LLLT on sciatic nerve regeneration after compression injury by means of the sciatic functional index (SFI) and Raman spectroscopy (RS). For this, 64 Wistar rats were divided into two groups according to the length of treatment: 14 days (n = 32) and 21 days (n = 32). These two groups were subdivided into four sub-groups of eight animals each (control 1; control 2; laser 660 nm; laser 808 nm). All animals had surgical exposure to the sciatic nerve, and only control 1 did not suffer nerve damage. To cause the lesion in the sciatic nerve, compression was applied with a Kelly clamp for 6 s. The evaluation of sensory deficit was performed by the painful exteroceptive sensitivity (PES) and neuromotor tests by the SFI. Laser 660 nm and laser 808 nm sub-groups were irradiated daily (100 mW, 40 s, energy density of 133 J/cm2). The sciatic nerve segment was removed for RS analysis. The animals showed accentuated sensory and neurofunctional deficit after injury and their rehabilitation occurred more effectively in the sub-groups treated with 660 nm laser. Control 2 sub-group did not obtain functional recovery of gait. The RS identified sphingolipids (718, 1065, and 1440 cm-1) and collagen (700, 852, 1004, 1270, and 1660 cm-1) as biomolecular characteristics of sciatic nerves. Principal component analysis revealed important differences among sub-groups and a directly proportional correlation with SFI, mainly in the sub-group laser 660 nm treated for 21 days. In the axonotmesis-type lesion model presented herein, the 660 nm laser was more efficient in neurofunctional recovery, and the Raman spectra of lipid and protein properties were attributed to the basic biochemical composition of the sciatic nerve.

Acute effect of high-definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial.

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called "conventional" tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg-1 min-1) were enrolled in this single-center, randomized, crossover, and sham-controlled trial. To test reliability, participants performed two time to exhaustion (TTE) tests (control conditions) on a cycle simulator with 80% of peak power until volitional exhaustion. Next, they randomly received HD-tDCS (2.4 mA), conventional (2.0 mA), or active sham tDCS (2.0 mA) over the motor cortex for 20-min before performing the TTE test. TTE, heart rate (HR), associative thoughts, peripheral (lower limbs), and whole-body ratings of perceived exertion (RPE) were recorded every minute. Outcome measures were reliable. There was no difference in TTE between HD-tDCS (853.1 ± 288.6 s), simulated conventional (827.8 ± 278.7 s), sham (794.3 ± 271.2 s), or control conditions (TTE1 = 751.1 ± 261.6 s or TTE2 = 770.8 ± 250.6 s) [F(1.95; 21.4) = 1.537; P = 0.24; η2p = 0.123]. There was no effect on peripheral or whole-body RPE and associative thoughts (P > 0.05). No serious adverse effect was reported. A single session of neither HD-tDCS nor conventional tDCS changed exercise performance and psychophysiological responses in athletes, suggesting that a ceiling effect may exist.

Development of a Classical Conditioning Task for Humans Examining Phasic Heart Rate Responses to Signaled Appetitive Stimuli: A Pilot Study.

Cardiac responses to appetitive stimuli have been studied as indices of motivational states and attentional processes, the former being associated with cardiac acceleration and latter deceleration. Very few studies have examined heart rate changes in appetitive classical conditioning in humans. The current study describes the development and pilot testing of a classical conditioning task to assess cardiac responses to appetitive stimuli and cues that reliably precede them. Data from 18 adults were examined. They were shown initially neutral visual stimuli (putative CS) on a computer screen followed by pictures of high-caloric food (US). Phasic cardiac deceleration to food images was observed, consistent with an orienting response to motivationally significant stimuli. Similar responses were observed to non-appetitive stimuli when they were preceded by the cue associated with the food images, suggesting that attentional processes were engaged by conditioned stimuli. These autonomic changes provide significant information about classical conditioning effects in humans.

Measurement of Active Motor Threshold Using a Dynamometer During Navigated Transcranial Magnetic Stimulation in a Patient with Postoperative Brain Tumor: Technical Note.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is being used for different purposes in patients with brain tumors. However, the procedure requires a positive electrophysiological response. For patients with negative response in rest conditions, active motor threshold (AMT) may be used. However, sometimes it is difficult to obtain AMT measures owing to inability of the patient to sustain steady muscle contraction. Herein, we describe a simple method by using a hand dynamometer to obtain AMT measures during nTMS session. CASE DESCRIPTION: A woman aged 68 years underwent total removal of a right frontal lobe oligodendroglioma World Health Organization grade II 15 years ago. Cranial magnetic resonance imaging during follow-up revealed local recurrence. In the postoperative period, she developed left upper limb paresis. A postoperative nTMS session was performed for motor electrophysiological evaluation. However, using the standard technique for AMT measurement, the patient was unable to perform sustained muscle contraction as required. A hand dynamometer was used. It allowed sustained muscle contraction for AMT measurement. A counter force for the index finger flexion, the hand support to stabilize hand joints, and a numerical screen serving for both the examiner and the patient as a feedback parameter may explain the success obtained with this simple device. CONCLUSIONS: Although more studies are necessary to validate the method, the hand dynamometer should be considered for patients unable to sustain muscle contraction during AMT measurement.

Computed tomography-guided navigated transcranial magnetic stimulation for preoperative brain motor mapping in brain lesion resection: A case report.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a well establish a noninvasive method for preoperative brain motor mapping. We commonly use magnetic resonance imaging (MRI) to supply the nTMS system. In some cases, MRI is not possible or available, and the use of computed tomography (CT) is necessary. We present the first report describing the association of CT and nTMS motor mapping for brain lesion resection. CASE DESCRIPTION: CT imaging of a 59-year-old man suffering from acquired immune deficiency syndrome for 17 years, presenting with seizure and right hemiparesis, revealed a small single hypodense ring-enhancing lesion in the left central sulci suggesting cerebral toxoplasmosis. After 3 weeks of neurotoxoplasmosis treatment, due to four consecutive tonic-clonic seizures, a new CT scan was performed and showed no lesion changes. MRI was in maintenance at that time. Infectious diseases department suggested a brain lesion biopsy. Due to lesion's location, we decided to perform a presurgical nTMS motor mapping. After a small craniotomy, we could precisely locate and safely totally remove the lesion. The pathology report revealed a high suspicious toxoplasmosis pattern. The patient was discharged after 2 days and continued toxoplasmosis treatment. After 6 months follow-up, he showed no signs of any procedure-related deficits or radiological recurrence. CONCLUSION: We report the feasibility and applicability of nTMS motor mapping using CT scan as an image source. It gives neurosurgeons another possibility to perform motor mapping for brain lesion removal, especially when MRI is not available or feasible.

Latin American and Caribbean consensus on noninvasive central nervous system neuromodulation for chronic pain management (LAC2-NIN-CP).

INTRODUCTION: Chronic pain (CP) is highly prevalent and generally undertreated health condition. Noninvasive brain stimulation may contribute to decrease pain intensity and influence other aspects related to CP. OBJECTIVE: To provide consensus-based recommendations for the use of noninvasive brain stimulation in clinical practice. METHODS: Systematic review of the literature searching for randomized clinical trials followed by consensus panel. Recommendations also involved a cost-estimation study. RESULTS: The systematic review wielded 24 transcranial direct current stimulation (tDCS) and 22 repetitive transcranial magnetic stimulation (rTMS) studies. The following recommendations were provided: (1) Level A for anodal tDCS over the primary motor cortex (M1) in fibromyalgia, and level B for peripheral neuropathic pain, abdominal pain, and migraine; bifrontal (F3/F4) tDCS and M1 high-definition (HD)-tDCS for fibromyalgia; Oz/Cz tDCS for migraine and for secondary benefits such as improvement in quality of life, decrease in anxiety, and increase in pressure pain threshold; (2) level A recommendation for high-frequency (HF) rTMS over M1 for fibromyalgia and neuropathic pain, and level B for myofascial or musculoskeletal pain, complex regional pain syndrome, and migraine; (3) level A recommendation against the use of anodal M1 tDCS for low back pain; and (4) level B recommendation against the use of HF rTMS over the left dorsolateral prefrontal cortex in the control of pain. CONCLUSION: Transcranial DCS and rTMS are recommended techniques to be used in the control of CP conditions, with low to moderate analgesic effects, and no severe adverse events. These recommendations are based on a systematic review of the literature and a consensus made by experts in the field. Readers should use it as part of the resources available to decision-making.

Behavioral adjustment to asymmetric reward availability among children with and without ADHD: effects of past and current reinforcement contingencies.

Altered reinforcement sensitivity is hypothesized to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Here we evaluate the behavioral sensitivity of Brazilian children with and without ADHD to a change in reward availability. Forty typically developing children and 32 diagnosed with DSM-IV ADHD completed a signal-detection task in which correct discriminations between two stimuli were associated with different frequencies of reinforcement. The response alternative associated with the higher rate of reinforcement switched, without warning, after 30 rewards were delivered. The task continued until another 30 rewards were delivered. Both groups of children developed a response bias toward the initially more frequently reinforced alternative. This effect was larger in the control group. The response allocation of the two groups changed following the shift in reward availability. Over time the ADHD group developed a significant response bias toward the now more frequently reinforced alternative. In contrast, the bias of the control group stayed near zero after an initial decline following the contingency change. The overall shift in bias was similar for the two groups. The behavior of both groups of children was sensitive to the asymmetric reward distribution and to the change in reward availability. Subtle group differences in response patterns emerged, possibly reflecting differences in the time frame of reward effects and sensitivity to reward exposure.

Conversion technique from neuroendoscopy to microsurgery in ventricular tumors: Technical note.

BACKGROUND: Ventricular tumors represent a major neurosurgical challenge, making endoscopic approach an invaluable tool as it gained importance due to technological advances. Nevertheless, the method is not exempt of risk and limitations, sometimes requiring an open surgery. Thus, initial measurements must be adopted in order to simplify an eventual need for conversion to open craniotomy. METHODS: Here, we describe a series of 6 patients with ventricular tumors approached by neuroendoscopy where the conversion to microsurgery turned out to be necessary. Patients' average age was 59.5 years (39-75 years). Average tumoral size was 17.8 mm (15-21 mm). There were 2 cases of lateral ventricle subependymoma and 4 cases of third ventricle colloid cysts. A standard surgical incision was performed in the coronal direction, allowing lateral expansion to 10 cm. Moreover, the endoscopic burr hole was enlarged to a 5 cm craniotomy. A small enlargement of the endoscopic cortical access was performed to gain a transcortical microsurgical corridor to the ventricular cavity. The need for conversion arose due to high consistency of the tumor (3 cases), technical problems (2 cases), and cortical collapse (1 case). RESULTS: There was one case of cerebrospinal fluid fistula and infection and one case of transitory memory disturbance. In both the cases, we obtained a complete functional recovery. Clinical and radiological follow-up showed total tumor removal with no recurrences. CONCLUSIONS: The technique herein described was easy to perform, promptly bypassed the endoscopic limitations, and gathered excellent surgical results. The possibility of adapting the method to other tumor locations may be considered.

Hydrocephalus caused by unilateral foramen of Monro obstruction: A review on terminology.

BACKGROUND: Hydrocephalus caused by unilateral foramen of Monro (FM) obstruction has been referred to in literature by many different terminologies. Precise terminology describing hydrocephalus confined to just one lateral ventricle has a very important prognostic value and determines whether or not the patient can be shunt free after an endoscopic procedure. METHODS: Aiming to define the best term for unilateral FM obstruction, 19 terms were employed on PubMed database (http://www.ncbi.nlm.nih.gov/pubmed) as quoted phrases. RESULTS: A total of 194 articles were found. Four patterns of hydrocephalus were discriminated as a result of our research term query and were divided by types for didactic purpose. Type A - partial dilation of the lateral ventricle; Type B - pure unilateral obstruction of the FM; Type C - previously shunted patients with secondary obstruction of the FM; and Type D - asymmetric lateral ventricles with patent FM. CONCLUSION: In unilateral FM obstruction hydrocephalus, an in-depth review on terminology application is critical to avoid mistakes that may compromise comparisons among different series. This terminology review suggests that Type B hydrocephalus, i.e., the hydrocephalus confined to just one lateral ventricle with no other sites of cerebrospinal fluid circulation blockage, are best described by the terms unilateral hydrocephalus (UH) and monoventricular hydrocephalus, the first being by far the most popular. Type A hydrocephalus is best represented in the literature by the terms uniloculated hydrocephalus and loculated ventricle; Type C hydrocephalus by the terms isolated lateral ventricle and isolated UH; and Type D hydrocephalus by the term asymmetric hydrocephalus.

Ontogenetic analysis of behavior in the tail suspension test: temporal differences in the emergence of within- and between-session habituation in Swiss mice.

Habituation is an important tool in the investigation of learning/memory throughout life. Despite that, few studies describe habituation from an ontogenetic perspective. Considering that, as soon as they are born, rodents can twist their bodies when lifted by their tails in an attempt to escape, this behavior should be well suited to study habituation behavior from birth to adulthood. Here, we implement a tail suspension test to study the ontogenetic development of habituation in Swiss mice. Our data indicate that a continuous within-session decrease in trunk movements can be observed from postnatal day (P) 10 onwards and that between-sessions habituation (from one day to another) can be observed from P16 onwards. Furthermore, we show that the adult pattern of within- and between-sessions reductions in activity is already present by the beginning of adolescence, at P28. Our results indicate that between-sessions habituation involves a more complex mechanism of memory and learning than within-session habituation, requiring a longer period of brain maturation before it can be displayed.

A pilot study on effects of 4×1 high-definition tDCS on motor cortex excitability.

High-Definition transcranial Direct Current Stimulation (HD-tDCS) using specialized small electrodes has been proposed as a focal, non-invasive neuromodulatory technique. Here we provide the first evidence of a change in cortical excitability after HD-tDCS of the motor cortex, using TMS motor evoked potential (MEP) as the measure of excitability. Stimulation for 20 minutes at 1 mA with an anode centered over the hand area of the motor cortex and four surrounding return electrodes (anodal 4×1 montage) produced a significant increase in MEP amplitude and variability after stimulation, compared to sham stimulation. Stimulation was well tolerated by all subjects with adverse effects limited to transient sensation under the electrodes. A high-resolution computational model confirmed predictions of increased focality using the 4×1 HD tDCS montage compared to conventional tDCS. Simulations also indicated that variability in placement of the center electrode relative to the location of the target (central sulcus) could account for increasing variability. These results provide support for the careful use of this technique where focal tDCS is desired.

Judgment of line orientation depends on gender, education, and type of error.

Visuospatial tasks are particularly proficient at eliciting gender differences during neuropsychological performance. Here we tested the hypothesis that gender and education are related to different types of visuospatial errors on a task of line orientation that allowed the independent scoring of correct responses ("hits", or H) and one type of incorrect responses ("commission errors", or CE). We studied 343 volunteers of roughly comparable ages and with different levels of education. Education and gender were significantly associated with H scores, which were higher in men and in the groups with higher education. In contrast, the differences between men and women on CE depended on education. We concluded that (I) the ability to find the correct responses differs from the ability to avoid the wrong responses amidst an array of possible alternatives, and that (II) education interacts with gender to promote a stable performance on CE earlier in men than in women.

Broca's aphemia: an illustrated account of its clinico-anatomic validity

OBJECTIVE: To present the case of a 54-year-old man with loss of speech, but with preservation of voluntary facio-lingual motility, language and other cognitive abilities (Broca's aphemia). METHOD: Observation of patient oral communicative abilities and general behavior, neuropsychological assessment and cranial computed tomography. RESULTS: Computed tomography showed a hyperdense lesion in the subcortex of the left precentral gyrus corresponding to Brodmann's area 6 and 44. Neuropsychological assessment confirmed that the major cognitive domains were intact. CONCLUSION: Our patient reiterates the validity of Broca's aphemia as a clinico-anatomic entity allowing us to portray it for the first time in pictures. From a neurobehavioral perspective, aphemia is related to apraxia rather than to aphasia, a fact that may have hampered the full grasp of its far-reaching implications for neurology and aphasiology.

OBJETIVO: Apresentar o caso de um paciente de 54 anos de idade com perda da fala, mas preservação da linguagem, das demais capacidades cognitivas, e da motilidade fácio-lingual voluntária (afemia de Broca). MÉTODO: Observação da capacidade de comunicação oral e do comportamento geral, exame neuropsicológico e tomografia computadorizada do crânio. RESULTADOS: A tomografia computadorizada revelou lesão hiperdensa no subcórtex do giro precentral esquerdo correspondendo às áreas 6 e 44 de Brodmann. O exame neuropsicológico confirmou que os principais domínios cognitivos se encontravam intactos. CONCLUSÃO: Nosso paciente reiterou a validade da afemia de Broca como entidade anátomo-clínico permitindo documentá-la em fotos pela primeira vez. Da perspectiva neurocomportamental, a afemia está vinculada às apraxias e não às afasias, o que pode ter prejudicado a apreensão plena do seu profundo significado para a neurologia e para a afasiologia.

Broca's aphemia: an illustrated account of its clinico-anatomic validity.

OBJECTIVE: To present the case of a 54-year-old man with loss of speech, but with preservation of voluntary facio-lingual motility, language and other cognitive abilities (Broca's aphemia). METHOD: Observation of patient oral communicative abilities and general behavior, neuropsychological assessment and cranial computed tomography. RESULTS: Computed tomography showed a hyperdense lesion in the subcortex of the left precentral gyrus corresponding to Brodmann's area 6 and 44. Neuropsychological assessment confirmed that the major cognitive domains were intact. CONCLUSION: Our patient reiterates the validity of Broca's aphemia as a clinico-anatomic entity allowing us to portray it for the first time in pictures. From a neurobehavioral perspective, aphemia is related to apraxia rather than to aphasia, a fact that may have hampered the full grasp of its far-reaching implications for neurology and aphasiology.

The self as a moral agent: linking the neural bases of social agency and moral sensitivity.

The human brain is inherently able to understand the world in moral ways, endowing most of us with an intuitive sense of fairness, concern for others, and observance of cultural norms. We have argued that this moral sensitivity ability depends on a sophisticated integration of cognitive, emotional, and motivational mechanisms, which are modulated by individual experience in different cultural milieus. Different lines of investigation on agency and morality have pointed to overlapping neural systems. Therefore, understanding the relationships between morality and agency may provide key insights into the mechanisms underlying human behavior in several clinical and societal settings. We used functional MRI to investigate the contribution of agency and of specific moral emotions to brain activation using action scripts. Results showed that emotionally neutral agency recruited neural networks previously associated with agency, intentionality and moral cognition, encompassing ventral and subgenual sectors of the medial prefrontal cortex (PFC), insula, anterior temporal cortex and superior temporal sulcus (STS). Compared to emotionally neutral agency, different categories of moral emotions led to distinct activation patterns: (1) prosocial emotions (guilt, embarrassment, compassion) activated the anterior medial PFC and STS, with (2) empathic emotions (guilt and compassion) additionally recruiting the mesolimbic pathway; (3) other-critical emotions (disgust and indignation) were associated with activation of the amygdala-parahippocampal and fusiform areas. These findings indicate that agency related to norm-abiding social behaviors of emotionally neutral scripts share neural substrates both with the "default mode" of brain function and with the moral sensitivity network. Additional activation in specific components of this network is elicited by different classes of moral emotions, in agreement with recent integrative models of moral cognition and emotion.

The moral affiliations of disgust: a functional MRI study.

Recent investigations in cognitive neuroscience have shown that ordinary human behavior is guided by emotions that are uniquely human in their experiential and interpersonal aspects. These "moral emotions" contribute importantly to human social behavior and derive from the neurobehavioral reorganization of the basic plan of emotions that pervade mammalian life. Disgust is one prototypic emotion with multiple domains that include viscerosomatic reaction patterns and subjective experiences linked to (a) the sensory properties of a class of natural stimuli, (b) a set of aversive experiences and (c) a unique mode of experiencing morality. In the current investigation, we tested the hypotheses that (a) the experience of disgust devoid of moral connotations ("pure disgust") can be subjectively and behaviorally differentiated from the experience of disgust disguised in the moral emotion of "indignation" and that (b) pure disgust and indignation may have partially overlapping neural substrates. Thirteen normal adult volunteers were investigated with functional magnetic resonance imaging as they read a series of statements depicting scenarios of pure disgust, indignation, and neutral emotion. After the scanning procedure, they assigned one basic and one moral emotion to each stimulus from an array of six basic and seven moral emotions. Results indicated that (a) emotional stimuli may evoke pure disgust with or without indignation, (b) these different aspects of the experience of disgust could be elicited by a set of written statements, and (c) pure disgust and indignation recruited both overlapping and distinct brain regions, mainly in the frontal and temporal lobes. This work underscores the importance of the prefrontal and orbitofrontal cortices in moral judgment and in the automatic attribution of morality to social events. Human disgust encompasses a variety of emotional experiences that are ingrained in frontal, temporal, and limbic networks.

Neonatal transection of the corpus callosum affects paw preference lateralization of adult Swiss mice.

In the present work, the hypothesis that the ontogenetic development of the corpus callosum (CC) affects the establishment of behavioral lateralization was tested by studying paw preference performance in adult Swiss mice that were subjected to mid-sagittal transection of the CC on the first postnatal day. Magnitude and direction of laterality were evaluated independently. No significant differences between groups were found for the magnitude of paw preference. On the other hand, the transected group presented a significant populational bias favoring the left paw that was not present in the control groups. These results lend support to the hypothesis that the development of the CC plays a role in the establishment of the normal pattern of behavioral lateralization.