Functional role of area 8A in the posterior dorsolateral frontal region of the human brain: A single case study.

Area 8A has traditionally been considered to be the frontal eye field (FEF), i.e. the area for the motor production of eye movements. However, recent research has shown that the FEF lies posteriorly in premotor area 6. Research in macaque monkeys has demonstrated that, in contrast to premotor area 6, which is involved in the production of motor actions, area 8A is implicated in the cognitive allocation of attention to stimuli based on instruction cues. The aim of the present study was to elucidate the specific cognitive role of area 8A by examining a unique patient with a lesion restricted to area 8A, i.e. sparing the premotor cortex. This right-handed male patient underwent neuropsychological assessment and testing on two conditional associative-learning tasks: the motor hand conditional associative-learning task (MCALT) assessing the selection of motor actions based on instruction cues and the visual conditional associative-learning task (VCALT) assessing the selection of visual stimuli based on instruction cues. The patient's performance on the VCALT was significantly impaired compared to control subjects, but performance on the MCALT and on an Eye Movement Control Task was preserved. The present study provides evidence that area 8A is critical for the cognitive process regulating the allocation of attention to different stimuli in the environment, but not in the production of eye movements. These findings enhance understanding of the functional organization of the posterior dorsolateral frontal region in the human brain and suggest a specialized role of area 8A in high-level cognitive processes.

A case of frontal lobe seizures with 'dancing-like' semiology.

BACKGROUND AND PURPOSE: 'Dancing-like' semiology is extremely rare and described in few case reports. It is characterized by rhythmic, oscillatory movements of the pelvis and/or limbs during which the subject appears to be dancing. It has been associated with both the frontal and temporal epileptic zone; however, the possible network involved in these fascinating seizures is unclear. METHODS: The case of a 45-year-old woman suffering from drug-resistant focal epilepsy with multi-day seizures of bizarre semiology is described. A structural and perfusion magnetic resonance imaging study (interictal and peri-ictal) and video-electroencephalograms were carried out, and several home videos were employed. A vagal stimulator was implanted. RESULTS: Home videos documented the 'dancing' semiology of seizures better than video- electroencephalogram recordings. The imaging study revealed a focal frontal polymicrogyria with a peri-ictal cerebral blood flow increase at the perisylvian lesion foci. The combination of add-on cenobamate and vagal nerve stimulation resulted in complete seizure freedom. CONCLUSION: The unusual and complex dancing-like semiology observed during our patient's seizures adds to the repertoire of fascinating complex motor manifestations of frontal lobe epilepsy.

DiSCIoser: unlocking recovery potential of arm sensorimotor functions after spinal cord injury by promoting activity-dependent brain plasticity by means of brain-computer interface technology: a randomized controlled trial to test efficacy.

BACKGROUND: Traumatic cervical spinal cord injury (SCI) results in reduced sensorimotor abilities that strongly impact on the achievement of daily living activities involving hand/arm function. Among several technology-based rehabilitative approaches, Brain-Computer Interfaces (BCIs) which enable the modulation of electroencephalographic sensorimotor rhythms, are promising tools to promote the recovery of hand function after SCI. The "DiSCIoser" study proposes a BCI-supported motor imagery (MI) training to engage the sensorimotor system and thus facilitate the neuroplasticity to eventually optimize upper limb sensorimotor functional recovery in patients with SCI during the subacute phase, at the peak of brain and spinal plasticity. To this purpose, we have designed a BCI system fully compatible with a clinical setting whose efficacy in improving hand sensorimotor function outcomes in patients with traumatic cervical SCI will be assessed and compared to the hand MI training not supported by BCI. METHODS: This randomized controlled trial will include 30 participants with traumatic cervical SCI in the subacute phase randomly assigned to 2 intervention groups: the BCI-assisted hand MI training and the hand MI training not supported by BCI. Both interventions are delivered (3 weekly sessions; 12 weeks) as add-on to standard rehabilitation care. A multidimensional assessment will be performed at: randomization/pre-intervention and post-intervention. Primary outcome measure is the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) somatosensory sub-score. Secondary outcome measures include the motor and functional scores of the GRASSP and other clinical, neuropsychological, neurophysiological and neuroimaging measures. DISCUSSION: We expect the BCI-based intervention to promote meaningful cortical sensorimotor plasticity and eventually maximize recovery of arm functions in traumatic cervical subacute SCI. This study will generate a body of knowledge that is fundamental to drive optimization of BCI application in SCI as a top-down therapeutic intervention, thus beyond the canonical use of BCI as assistive tool. TRIAL REGISTRATION: Name of registry: DiSCIoser: improving arm sensorimotor functions after spinal cord injury via brain-computer interface training (DiSCIoser). TRIAL REGISTRATION NUMBER: NCT05637775; registration date on the ClinicalTrial.gov platform: 05-12-2022.

Sulci and gyri are topological cerebral landmarks in individual subjects: a study of brain navigation during tumour resection.

Surgical resection of brain tumours aims at the maximal safe resection of the pathological tissue with minimal functional impairment. To achieve this objective, reliable anatomical landmarks are indispensable to navigate into the brain. The neuronavigation system can provide information to target the location of the patient's lesion, but after the craniotomy, a brain shift and relaxation mismatch with it often occur. By contrast, sulci/gyri are topological cerebral landmarks in individual patients and do shift with the brain parenchyma during lesion removal, but remain independent from brain shift in relation to the sulci/gyri. Here, we present a case report of a novel strategy based on anatomical landmarks to guide intraoperative brain tumour resection, without using a standard neuronavigation system. A preoperative brain mapping of the peri-tumoural sulci by the MRI and surface reconstruction was followed by confirmation of the anatomical landmarks for the motor cortex using navigated transcranial magnetic stimulation. The resulting location was used as a seed for diffusion tensor imaging tractography to reconstruct the corticospinal tracts. These selected cortical landmarks (sulci/gyri) delimited the margins of the two lesions and the specific location under which the corticospinal tract courses, thus facilitating monitoring of the peri-tumoural region during brain resection. In this case, 96% of the brain tumour from the pericentral somatomotor region was successfully removed without chronic post-operative motor impairments. This approach is based on cortical anatomy that is fixed during surgery and does not suffer from the brain shift that could misplace the lesion according to the neuronavigation system.

The Precentral Insular Cortical Network for Speech Articulation.

Apraxia of speech is a motor disorder characterized by the impaired ability to coordinate the sequential articulatory movements necessary to produce speech. The critical cortical area(s) involved in speech apraxia remain controversial because many of the previously reported cases had additional aphasic impairments, preventing localization of the specific cortical circuit necessary for the somatomotor execution of speech. Four patients with "pure speech apraxia" (i.e., who had no aphasic and orofacial motor impairments) are reported here. The critical lesion in all four patients involved, in the left hemisphere, the precentral gyrus of the insula (gyrus brevis III) and, to a lesser extent, the nearby areas with which it is strongly connected: the adjacent subcentral opercular cortex (part of secondary somatosensory cortex) and the most inferior part of the central sulcus where the orofacial musculature is represented. There was no damage to rostrally adjacent Broca's area in the inferior frontal gyrus. The present study demonstrates the critical circuit for the coordination of complex articulatory movements prior to and during the execution of the motor speech plans. Importantly, this specific cortical circuit is different from those that relate to the cognitive aspects of language production (e.g., Broca's area on the inferior frontal gyrus).

Provocation and prediction of visual peripersonal neglect-like symptoms in preoperative planning and during awake brain surgery.

Neglect is a severe neuropsychological/neurological deficit that usually develops due to lesions of the posterior inferior parietal area of the right hemisphere and is characterized by a lack of attention to the left side. Our case is a proven right-handed, 30-year-old female patient with a low-grade glioma, which was located in the temporo-opercular region and also in the superior temporal gyrus of the right hemisphere. Upon presurgical planning, the motor, language, and visuospatial functions were mapped. In order to achieve this, the protocol for routine magnetic resonance imaging and navigated transcranial magnetic stimulation has been expanded, accordingly.

Binaural Beats Reduce Postoperative Morphine Consumption in Older adults After Total Knee Replacement Surgery.

CONTEXT: A reduction in the use of opioids by older adult patients could reduce unpleasant side effects for them. During general anesthesia, binaural beat (BB) listening has been found to reduce intraoperative fentanyl consumption as well as postoperative pain scores and discharge time. Auditory BBs are a perceptual phenomenon occurring when tones of 2 slightly different frequencies are presented simultaneously and separately to each ear. OBJECTIVE: The study intended to evaluate the ability of BBs, as a nonpharmacological premedication, to reduce postoperative morphine consumption in older adults undergoing total knee replacement surgery and to modify the levels of anxiety and feelings of pain that patients experience. DESIGN: The research team designed a prospective, single-center, randomized controlled study. SETTING: The study was conducted in the Orthopedic Department of the Santa Maria Maddalena Hospital (Volterra [Pisa], Italy). PARTICIPANTS: Forty older adults at the hospital who were undergoing total knee joint replacement with spinal anesthesia participated in the study. INTERVENTION: The study included 2 groups (n = 20 each), one receiving BBs stimulation with frequencies of 256 Hz in one ear and 260 Hz in the opposite ear producing a BB of 4 Hz (intervention group), and the other receiving acoustical stimulation at 256 Hz in both ears (control group). BBs, or acoustical stimulation, were administered before the surgical procedure. Both acoustical stimuli, generated with the Gnaural program, were delivered through stereo headphones connected to a laptop in the preoperative holding area. OUTCOME MEASURES: The study measured postoperative, cumulative, self-administered morphine consumption, in mg, through a patient-controlled analgesia device. Feelings of anxiety were also assessed using the State-Trait Anxiety Inventory, and feelings of pain were measured every 8 h during the first postoperative day using a numerical rating scale. RESULTS: Patients who received the intervention, consumed almost half of the dosage of morphine during the first postoperative day when compared with the control group's consumption, 5.75 mg ± 5.25 vs 11.85 mg ± 7.71, respectively. The consumption did not correlate to anxiety measures. Regarding pain perception, no differences between the groups were captured. CONCLUSIONS: BB stimulation before surgery can be successfully used as a nonpharmacological treatment to reduce morphine consumption in older adults who undergo knee replacement. The use of a noninvasive, safe, and inexpensive BB intervention can result in a positive effect on patients' postoperative recovery.

The Hemispheric Distribution of α-Band EEG Activity During Orienting of Attention in Patients with Reduced Awareness of the Left Side of Space (Spatial Neglect).

EEG studies in healthy humans have highlighted that alpha-band activity is relatively reduced over the occipital-parietal areas of the hemisphere contralateral to the direction of spatial attention. Here, we investigated the hemispheric distribution of alpha during orienting of attention in male and female right brain-damaged patients with left spatial neglect. Temporal spectral evolution showed that in patients with neglect alpha oscillations over the damaged hemisphere were pathologically enhanced both during the baseline-fixation period that preceded cued orienting (capturing tonic alpha changes) and during orienting with leftward, rightward, or neutral-bilateral spatial cues (reflecting phasic alpha changes). Patients without neglect showed a similar though significantly less enhanced hemispheric asymmetry. Healthy control subjects displayed a conventional decrease of alpha activity over the hemisphere contralateral to the direction of orienting. In right-brain-damaged patients, neglect severity in the line bisection task was significantly correlated both with tonic alpha asymmetry during the baseline period and with phasic asymmetries during orienting of attention with neutral-bilateral and leftward cues. Asymmetries with neutral-bilateral and leftward cues were correlated with lesion of white matter tracts linking frontal with parietal-occipital areas. These findings show that disruption of rostrocaudal white matter connectivity in the right hemisphere interferes with the maintenance of optimal baseline tonic levels of alpha and the phasic modulation of alpha activity during shifts of attention. The hemispheric distribution of alpha activity can be used as a diagnostic tool for acquired pathological biases of spatial attention due to unilateral brain damage.SIGNIFICANCE STATEMENT Alpha desynchronization over the hemisphere contralateral to the attended side of space is a reliable marker of attentional orienting in the healthy human brain: can the same marker be used to spot and quantify acquired disturbances of spatial attention after unilateral brain injuries? Are pathological modifications in the hemispheric distribution of alpha specifically linked to attentional neglect for one side of space? We show that in patients with right brain damage the pathological enhancement of alpha oscillations over the parietal and occipital areas of the injured hemisphere is correlated with reduced awareness for the left side of space and with the lesion of white matter pathways that subserve frontal modulation of alpha activity in posterior brain areas.

EEG Correlates of Preparatory Orienting, Contextual Updating, and Inhibition of Sensory Processing in Left Spatial Neglect.

Studies with event-related potentials have highlighted deficits in the early phases of orienting to left visual targets in right-brain-damaged patients with left spatial neglect (N+). However, brain responses associated with preparatory orienting of attention, with target novelty and with the detection of a match/mismatch between expected and actual targets (contextual updating), have not been explored in N+. Here in a study in healthy humans and brain-damaged patients of both sexes we demonstrate that frontal activity that reflects supramodal mechanisms of attentional orienting (Anterior Directing Attention Negativity, ADAN) is entirely spared in N+. In contrast, posterior responses that mark the early phases of cued orienting (Early Directing Attention Negativity, EDAN) and the setting up of sensory facilitation over the visual cortex (Late Directing Attention Positivity, LDAP) are suppressed in N+. This uncoupling is associated with damage of parietal-frontal white matter. N+ also exhibit exaggerated novelty reaction to targets in the right side of space and reduced novelty reaction for those in the left side (P3a) together with impaired contextual updating (P3b) in the left space. Finally, we highlight a drop in the amplitude and latency of the P1 that over the left hemisphere signals the early blocking of sensory processing in the right space when targets occur in the left one: this identifies a new electrophysiological marker of the rightward attentional bias in N+. The heterogeneous effects and spatial biases produced by localized brain damage on the different phases of attentional processing indicate relevant functional independence among their underlying neural mechanisms and improve the understanding of the spatial neglect syndrome.SIGNIFICANCE STATEMENT Our investigation answers important questions: are the different components of preparatory orienting (EDAN, ADAN, LDAP) functionally independent in the healthy brain? Is preparatory orienting of attention spared in left spatial neglect? Does the sparing of preparatory orienting have an impact on deficits in reflexive orienting and in the assignment of behavioral relevance to the left space? We show that supramodal preparatory orienting in frontal areas is entirely spared in neglect patients though this does not counterbalance deficits in preparatory parietal-occipital activity, reflexive orienting, and contextual updating. This points at relevant functional dissociations among different components of attention and suggests that improving voluntary attention in N+ might be behaviorally ineffective unless associated with stimulations boosting the response of posterior parietal-occipital areas.

Progression from Vegetative to Minimally Conscious State Is Associated with Changes in Brain Neural Response to Passive Tasks: A Longitudinal Single-Case Functional MRI Study.

OBJECTIVES: Functional magnetic resonance imaging (fMRI) may be adopted as a complementary tool for bedside observation in the disorders of consciousness (DOC). However, the diagnostic value of this technique is still debated because of the lack of accuracy in determining levels of consciousness within a single patient. Recently, Giacino and colleagues (2014) hypothesized that a longitudinal fMRI evaluation may provide a more informative assessment in the detection of residual awareness. The aim of this study was to measure the correspondence between clinically defined level of awareness and neural responses within a single DOC patient. METHODS: We used a follow-up fMRI design in combination with a passive speech-processing task. Patient's consciousness was measured through time by using the Coma Recovery Scale. RESULTS: The patient progressed from a vegetative state (VS) to a minimally conscious state (MCS). Patient's task-related neural responses mirrored the clinical change from a VS to an MCS. Specifically, while in an MCS, but not a VS, the patient showed a selective recruitment of the left angular gyrus when he listened to a native speech narrative, as compared to the reverse presentation of the same stimulus. Furthermore, the patient showed an increased response in the language-related brain network and a greater deactivation in the default mode network following his progression to an MCS. CONCLUSIONS: Our findings indicate that longitudinal assessment of brain responses to passive stimuli can contribute to the definition of the clinical status in individual patients with DOC and represents an adequate counterpart of the bedside assessment during the diagnostic decision-making process. (JINS, 2016, 22, 620-630).

Deep Brain Stimulation of the Anterior Limb of the Internal Capsule May Be Efficacious for Explosive Aggressive Behaviour.

BACKGROUND: Intermittent explosive disease (IED) is a psychiatric disorder characterized by intermittent attacks of rage and violence frequently resistant to pharmacological therapy. Deep brain stimulation (DBS) of the posteromedial hypothalamus has been applied with fair results and clinical improvement with some surgical morbidity due to neurovegetative side effects. The anterior limb of the internal capsule/ventral capsule/ventral striatum (VC/VS) has never been used alone as a target for this disease. OBJECTIVES: The aim of this study is to evaluate the efficacy of bilateral DBS of the VC/VS for the treatment of IED. METHODS: We performed bilateral DBS of the VC/VS in a 21-year-old patient with IED. This young man had a traumatic birth complicated by hypoxia, and he showed a mild mental impairment. Different pharmacological treatments were carried out with no results before DBS was proposed to the patient's relatives after multidisciplinary approval. RESULTS: After 22 months of high-frequency monopolar bilateral DBS of the VC/VS, the patient showed a significant improvement. Postoperative 18F-FDG PET-CT studies ruled out a reduction of the hypermetabolic areas located in the limbic system previously detected in pre-operative investigations. CONCLUSIONS: Bilateral DBS of the VC/VS may be considered for the treatment of IED without the risk of neurovegetative side effects.

Neuropsychological Testing in Interventional Cardiology Staff after Long-Term Exposure to Ionizing Radiation.

This study aimed at comparing neuropsychological test scores in 83 cardiologists and nurses (exposed group, EG) working in the cardiac catheterization laboratory, and 83 control participants (non exposed group, nEG), to explore possible cognitive impairments. The neuropsychological assessment was carried out by means of a battery called "Esame Neuropsicologico Breve." EG participants showed significantly lower scores on the delayed recall, visual short-term memory, and semantic lexical access ability than the nEG ones. No dose response could be detected. EG participants showed lower memory and verbal fluency performances, as compared with nEG. These reduced skills suggest alterations of some left hemisphere structures that are more exposed to IR in interventional cardiology staff. On the basis of these findings, therefore, head protection would be a mandatory good practice to reduce effects of head exposure to ionizing radiation among invasive cardiology personnel (and among other exposed professionals).

Damage to white matter pathways in subacute and chronic spatial neglect: a group study and 2 single-case studies with complete virtual "in vivo" tractography dissection.

The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.

Association between the morphological features of the central sulcus and the somatomotory representation: anatomo-functional evaluation of neuroplasticity through nTMS.

In recent years navigated transcranial magnetic stimulation (nTMS) has emerged as a useful tool for the preoperative mapping of brain cortical areas surrounding neoplastic tissues allowing for maximal safe tumor resection and minimizing new postoperative permanent neurological deficits. Three patients presenting with an intrinsic brain tumor (one metastasis from mammary carcinoma, one high-grade glioma, and one low-grade glioma) located within or in close relationship to the central sulcus were enrolled for this study. The MRI-based morphological and nTMS mapping of the central sulcus of the intact hemisphere was complemented by the examination of the contralateral region harboring the lesion. The findings were independently compared, in search of evidence of tumor-induced neuroplasticity and/or signs of parenchymal dislocation/infiltration caused by the tumor. An individual description of each mapping session is provided. Significant discrepancies were observed between morphological MRI and functional nTMS mapping in two patients, demonstrating a tumor-induced shift of distinct cortical areas controlling hand and/or facial movements. In the cases of gliomas, a lower MT was detected in the lesioned hemisphere, possibly due to increased electrical excitability caused by the tumor itself. The integration of MRI-based morphological mapping of the central sulcus with the detection of its somatomotor representations through nTMS can assist neurosurgeons when planning the resection of a motor-eloquent tumor, stratifying the risks of secondary neurological deficits. The combination of the two preoperative techniques is able to disclose tumor-induced neural plasticity subsequently guiding a more precise resection.

Virtual Reality Exposure Therapy for Treating Fear of Contamination Disorders: A Systematic Review of Healthy and Clinical Populations.

Virtual Reality Exposure Therapy (VRET), particularly immersive Virtual Reality Exposure Therapy (iVRET), has gained attraction as an innovative approach in exposure therapy (ET), notably for some anxiety disorders with a fear of contamination component, such as spider phobia (SP) and obsessive-compulsive disorder (OCD). This systematic work investigates iVRET's effectiveness in modulating disgust emotion-a shared aberrant feature across these disorders. Recent reviews have evaluated VRET's efficacy against in vivo ET. However, emerging evidence also highlights iVRET's potential in diminishing atypical disgust and related avoidance behaviors, expanding beyond traditional fear-focused outcomes. Our systematic synthesis, adhering to PRISMA guidelines, aims to fill this gap by assessing iVRET's efficacy in regulating disgust emotion within both clinical and at-risk populations, identified through standardized questionnaires and subjective disgust ratings. This research analyzes data from eight studies on clinical populations and five on healthy populations, offering an insight into iVRET's potential to mitigate the aberrant disgust response, a common transdiagnostic feature in varied psychopathologies. The findings support iVRET's clinical relevance in disgust management, providing evidence for a broader therapeutic application of iVRET and pointing out the need for more focused and complete investigations in this emergent field.

Evolution of Severe Closed Head Injury: Assessing Ventricular Volume and Behavioral Measures at 30 and 90 Days Post-Injury.

Background: Assessing functional outcomes in Severe Closed Head Injury (SCHI) is complex due to brain parenchymal changes. This study examines the Ventricles to Intracranial Volume Ratio (VBR) as a metric for these changes and its correlation with behavioral scales. Methods: Thirty-one SCHI patients were included. VBR was derived from CT scans at 3, 30, and 90 days post-injury and compared with Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) assessments at 30 and 90 days. Results: Ten patients were excluded post-decompressive craniectomy or ventriculoperitoneal shunt. Findings indicated a VBR decrease at 3 days, suggesting acute phase compression, followed by an increase from 30 to 90 days, indicative of post-acute brain atrophy. VBR correlated positively with the Marshall score in the initial 72 h, positioning it as an early indicator of subsequent brain atrophy. Nevertheless, in contrast to the Marshall score, VBR had stronger associations with DRS and ERBI at 90 days. Conclusions: VBR, alongside behavioral assessments, presents a robust framework for evaluating SCHI progression. It supports early functional outcome correlations informing therapeutic approaches. VBR's reliability underscores its utility in neurorehabilitation for ongoing SCHI assessment and aiding clinical decisions.

No inherent left and right side in human 'mental number line': evidence from right brain damage.

Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial, imagery or object-centred neglect and that it rather depends on disruption of an abstract non-spatial representation of small numerical magnitudes.

Alexithymia and asthma: a systematic review.

Growing evidence from scientific research elucidates the important role of alexithymia in chronic immune diseases. This Review aims to explore the presence of alexithymia in patients affected by asthma and clarify its associations with other involved psychological and physical factors. In January 2023, according to PRISMA guidelines, a systematic search using PubMed and Scopus was conducted. Twenty-six studies were eligible based on inclusion criteria. Alexithymia was significantly present in asthma patients, with most studies reporting a higher prevalence (from 9 to 62.8%) than in control groups (approximately 10%). The coexistence of asthma and alexithymia was associated with a worse quality of life, psychiatric comorbidity, poor symptom control, and difficulty in recognizing exacerbations of the disease. These results suggest that alexithymia can negatively impact the management of asthma. For this reason, we recommend an accuracy assessment in clinical settings and the implementation of psychological interventions to promote the emotional and physical wellbeing of asthmatic patients.

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.