The parietal architecture binding cognition to sensorimotor integration: a multimodal causal study.

Despite human's praxis abilities are unique among primates, comparative observations suggest that these cognitive motor skills could have emerged from exploitation and adaptation of phylogenetically older building blocks, namely the parieto-frontal networks subserving prehension and manipulation. Within this framework, investigating to which extent praxis and prehension-manipulation overlap and diverge within parieto-frontal circuits could help in understanding how human cognition shapes hand actions. This issue has never been investigated by combining lesion mapping and direct electrophysiological approaches in neurosurgical patients. To this purpose, 79 right-handed left-brain tumour patient candidates for awake neurosurgery were selected based on inclusion criteria. First, a lesion mapping was performed in the early postoperative phase to localize the regions associated with an impairment in praxis (imitation of meaningless and meaningful intransitive gestures) and visuo-guided prehension (reaching-to-grasping) abilities. Then, lesion results were anatomically matched with intraoperatively identified cortical and white matter regions, whose direct electrical stimulation impaired the Hand Manipulation Task. The lesion mapping analysis showed that prehension and praxis impairments occurring in the early postoperative phase were associated with specific parietal sectors. Dorso-mesial parietal resections, including the superior parietal lobe and precuneus, affected prehension performance, while resections involving rostral intraparietal and inferior parietal areas affected praxis abilities (covariate clusters, 5000 permutations, cluster-level family-wise error correction P < 0.05). The dorsal bank of the rostral intraparietal sulcus was associated with both prehension and praxis (overlap of non-covariate clusters). Within praxis results, while resection involving inferior parietal areas affected mainly the imitation of meaningful gestures, resection involving intraparietal areas affected both meaningless and meaningful gesture imitation. In parallel, the intraoperative electrical stimulation of the rostral intraparietal and the adjacent inferior parietal lobe with their surrounding white matter during the hand manipulation task evoked different motor impairments, i.e. the arrest and clumsy patterns, respectively. When integrating lesion mapping and intraoperative stimulation results, it emerges that imitation of praxis gestures first depends on the integrity of parietal areas within the dorso-ventral stream. Among these areas, the rostral intraparietal and the inferior parietal area play distinct roles in praxis and sensorimotor process controlling manipulation. Due to its visuo-motor 'attitude', the rostral intraparietal sulcus, putative human homologue of monkey anterior intraparietal, might enable the visuo-motor conversion of the observed gesture (direct pathway). Moreover, its functional interaction with the adjacent, phylogenetic more recent, inferior parietal areas might contribute to integrate the semantic-conceptual knowledge (indirect pathway) within the sensorimotor workflow, contributing to the cognitive upgrade of hand actions.

Stimulation of frontal pathways disrupts hand muscle control during object manipulation.

The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output but, despite extensive investigation in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in 34 patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tract disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution at 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: (i) an 'arrest' pattern, characterized by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local middle U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. (ii) a 'clumsy' pattern, characterized by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (P = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and postoperative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

Distinct Functional and Structural Connectivity of the Human Hand-Knob Supported by Intraoperative Findings.

Fine motor skills rely on the control of hand muscles exerted by a region of primary motor cortex (M1) that has been extensively investigated in monkeys. Although neuroimaging enables the exploration of this system also in humans, indirect measurements of brain activity prevent causal definitions of hand motor representations, which can be achieved using data obtained during brain mapping in tumor patients. High-frequency direct electrical stimulation delivered at rest (HF-DES-Rest) on the hand-knob region of the precentral gyrus has identified two sectors showing differences in cortical excitability. Using quantitative analysis of motor output elicited with HF DES-Rest, we characterized two sectors based on their excitability, higher in the posterior and lower in the anterior sector. We studied whether the different cortical excitability of these two regions reflected differences in functional connectivity (FC) and structural connectivity (SC). Using healthy adults from the Human Connectome Project (HCP), we computed FC and SC of the anterior and the posterior hand-knob sectors identified within a large cohort of patients. The comparison of FC of the two seeds showed that the anterior hand-knob, relative to the posterior hand-knob, showed stronger functional connections with a bilateral set of parietofrontal areas responsible for integrating perceptual and cognitive hand-related sensorimotor processes necessary for goal-related actions. This was reflected in different patterns of SC between the two sectors. Our results suggest that the human hand-knob is a functionally and structurally heterogeneous region organized along a motor-cognitive gradient.SIGNIFICANCE STATEMENT The capability to perform complex manipulative tasks is one of the major characteristics of primates and relies on the fine control of hand muscles exerted by a highly specialized region of the precentral gyrus, often termed the "hand-knob" sector. Using intraoperative brain mapping, we identify two hand-knob sectors (posterior and anterior) characterized by differences in cortical excitability. Based on resting-state functional connectivity (FC) and tractography in healthy subjects, we show that posterior and anterior hand-knob sectors differ in their functional connectivity (FC) and structural connectivity (SC) with frontoparietal regions. Thus, anteroposterior differences in cortical excitability are paralleled by differences in FC and SC that likely reflect a motor (posterior) to cognitive (anterior) organization of this cortical region.

Motor impairment evoked by direct electrical stimulation of human parietal cortex during object manipulation.

In primates, the parietal cortex plays a crucial role in hand-object manipulation. However, its involvement in object manipulation and related hand-muscle control has never been investigated in humans with a direct and focal electrophysiological approach. To this aim, during awake surgery for brain tumors, we studied the impact of direct electrical stimulation (DES) of parietal lobe on hand-muscles during a hand-manipulation task (HMt). Results showed that DES applied to fingers-representation of postcentral gyrus (PCG) and anterior intraparietal cortex (aIPC) impaired HMt execution. Different types of EMG-interference patterns were observed ranging from a partial (task-clumsy) or complete (task-arrest) impairment of muscles activity. Within PCG both patterns coexisted along a medio (arrest)-lateral (clumsy) distribution, while aIPC hosted preferentially the task-arrest. The interference patterns were mainly associated to muscles suppression, more pronounced in aIPC with respect to PCG. Moreover, within PCG were observed patterns with different level of muscle recruitment, not reported in the aIPC. Overall, EMG-interference patterns and their probabilistic distribution suggested the presence of different functional parietal sectors, possibly playing different roles in hand-muscle control during manipulation. We hypothesized that task-arrest, compared to clumsy patterns, might suggest the existence of parietal sectors more closely implicated in shaping the motor output.

Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation.

Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.

Large scale networks for human hand-object interaction: Functionally distinct roles for two premotor regions identified intraoperatively.

The development of awake intraoperative brain-mapping procedures for resection of brain tumors is of growing interest in neuroscience, because it enables direct testing of brain tissue, previously only possible in non-human primates. In a recent study performed in this setting specific effects can be induced by direct electrical stimulation on different sectors of premotor cortex during the execution of a hand manipulation task. Specifically, direct electrical stimulation applied on a dorsal sector of precentral cortex led to an increase in motor unit recruitment in hand muscles during execution of a hand manipulation task (Recruitment sector). The opposite effect was elicited when electrical stimulation was delivered more ventrally on the precentral cortex (Suppression sector). We studied whether the different effects on motor behavior induced by direct electrical stimulation applied on the two sites of the precentral cortex underlie differences in their functional connectivity with other brain areas, measured using resting state fMRI. Using healthy adults scanned as part of the Human Connectome Project, we computed the functional connectivity of each sector used as seeds. The functional connectivity patterns of the two intraoperative seeds was similar but cross-comparison revealed that the left and right Recruitment sectors had stronger functional connections with the hand region of the sensorimotor cortex, while the right Suppression region displayed stronger functional connectivity with a bilateral set of parieto-frontal areas crucial for the integration of perceptual and cognitive hand-related sensorimotor processes required for goal-related hand actions. Our results suggest that analyzing data obtained in the intraoperative setting with resting state functional magnetic resonance imaging in healthy brains can yield useful insight into the roles of different premotor sectors directly involved in hand-object interaction.

Frontal pathways in cognitive control: direct evidence from intraoperative stimulation and diffusion tractography.

A key aspect of cognitive control is the management of conflicting incoming information to achieve a goal, termed 'interference control'. Although the role of the right frontal lobe in interference control is evident, the white matter tracts subserving this cognitive process remain unclear. To investigate this, we studied the effect of transient network disruption (by means of direct electrical stimulation) and permanent disconnection (resulting from neurosurgical resection) on interference control processes, using the Stroop test in the intraoperative and extraoperative neurosurgical setting. We evaluated the sites at which errors could be produced by direct electrical stimulation during an intraoperative Stroop test in 34 patients with frontal right hemisphere glioma. Lesion-symptom mapping was used to evaluate the relationship between the resection cavities and postoperative performance on the Stroop test of this group compared with an additional 29 control patients who did not perform the intraoperative test (63 patients in total aged 17-77 years; 28 female). We then examined tract disruption and disconnection in a subset of eight patients who underwent both the intraoperative Stroop test and high angular resolution diffusion imaging (HARDI) tractography. The results showed that, intraoperatively, the majority of sites associated with errors during Stroop test performance and concurrent subcortical stimulation clustered in a region of white matter medial to the right inferior frontal gyrus, lateral and superior to the striatum. Patients who underwent the intraoperative test maintained cognitive control ability at the 1-month follow-up (P = 0.003). Lesion-symptom analysis showed resection of the right inferior frontal gyrus was associated with slower postoperative Stroop test ability (corrected for multiple comparisons, 5000 permutations). The stimulation sites associated with intraoperative errors most commonly corresponded with the inferior fronto-striatal tracts and anterior thalamic radiation (over 75% of patients), although the latter was commonly resected without postoperative deficits on the Stroop test (in 60% of patients). Our results show converging evidence to support a critical role for the inferior frontal gyrus in interference control processes. The intraoperative data combined with tractography suggests that cortico-subcortical tracts, over cortico-cortical connections, may be vital in maintaining efficiency of cognitive control processes. This suggests the importance of their preservation during resection of right frontal tumours.

Attention and cognitive load modulate motor resonance during action observation.

Observation of others' actions evokes a motor resonant (MR) response, in the parieto-frontal Action Observation Network (AON, comprising BA40, BA6, BA4). In order to investigate the effect of cognitive processes on the AON we manipulated attention and cognitive load during central and peripheral observation of hand grasping actions with three experiments. Motor Evoked Potentials (MEPs) were elicited in the opponent of the thumb (OP) and abductor of the little finger (ADM) by Transcranial Magnetic Stimulation (TMS) of the primary motor cortex. First, we investigated the role of selective attention by asking subjects to focus their attention on the thumb of the moving hand in central vision. A selective facilitation of OP MEPs was recorded, without the expected ADM MEPs modulation. Second, a "covert attention" paradigm was used to investigate the role of attention in peripheral vision. Surprisingly, MEP modulation was virtually abolished. In the third experiment we tested the hypothesis that the higher cognitive load introduced by the covert attention instruction had interfered with MR. We allowed subjects to view the action before its peripheral presentation with covert attention, thereby decreasing the cognitive effort necessary to decode the grasping action. The accuracy of motor resonant response was restored.

The mirror neuron system and the strange case of Broca's area.

Mirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess "mirror" properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech.

What you see is what you get: motor resonance in peripheral vision.

Observation of others' actions evokes a subliminal motor resonant response, which reflects the motor program encoding observed actions. The possibility that actions located in the peripheral field of vision may also activate motor resonant responses has not been investigated. We examine the excitability modulation of motor pathways in response to grasping actions viewed in near peripheral vision; results are directly compared to responses to the same actions viewed in central vision (Borroni et al. in Eur J Neurosci 34:662-669, 2011. doi: 10.1111/j.1460-9568.2011.07779.x ). We hypothesize that actions observed in peripheral vision are effective in modulating the excitability of motor pathways, but that responses have a low kinematic specificity. While the neural resources of central vision provide the most accurate perception of biological motion, the decreased visual acuity in periphery may be sufficient to discriminate only general aspects of movement and perhaps to recognize the gist of visual scenes. Right-handed subjects observed a video of two grasping actions at 10° eccentricity in the horizontal plane. Motor-evoked potentials were elicited in the right OP and ADM muscles by TMS of the left primary motor cortex at different delays during the observed actions. Results show that actions viewed in near peripheral vision are effective in modulating the subliminal activation of motor circuits, but that responses are rough and inaccurate, and do not reflect the motor program encoding the observed action or its goal. We suggest that due to their limited kinematic accuracy, these subliminal motor responses may provide information about the general aspects of observed actions, rather than their specific execution.

Object-oriented hand dexterity and grasping abilities, from the animal quarters to the neurosurgical OR: a systematic review of the underlying neural correlates in non-human, human primate and recent findings in awake brain surgery.

Introduction: The sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping. Methods: A systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate. Results: We provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection. Discussion: The anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.

Transcranial versus direct electrical stimulation for intraoperative motor-evoked potential monitoring: Prognostic value comparison in asleep brain tumor surgery.

Objective: Safe resection of gliomas involving motor pathways in asleep-anesthesia requires the combination of brain mapping, to identify and spare essential motor sites, and continuous monitoring of motor-evoked potentials (MEPs), to detect possible vascular damage to the corticospinal tract (CST). MEP monitoring, according to intraoperative neurophysiology societies, is generally recommended by transcranial electrodes (TES), and no clear indications of direct cortical stimulation (DCS) or the preferential use of one of the two techniques based on the clinical context is available. The main aim of the study was to identify the best technique(s) based on different clinical conditions, evaluating the efficacy and prognostic value of both methodologies. Methods: A retrospective series of patients with tumors involving the motor pathways who underwent surgical resection with the aid of brain mapping and combined MEP monitoring via TES and DCS was evaluated. Irreversible MEP amplitude reduction (>50% compared to baseline) was used as an intraoperative warning and correlated to the postoperative motor outcome. Selectivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed for both techniques. Results: Four hundred sixty-two patients were retrospectively analyzed, and only 1.9% showed a long-term motor impairment. Both TES and DCS obtained high specificity and NPV for the acute and 1-month motor deficit. Sensitivity was rather low for the acute deficit but excellent considering the 1-month follow-up for both techniques. DCS was extremely reliable in predicting a postoperative motor decline (PPV of 100% and 90% for acute and long-term deficit, respectively). Conversely, TES produced a high number of false-positive results, especially for long-term deficits (65, 87.8% of all warnings) therefore obtaining poor PPV values (18% and 12% for acute and 1-month deficits, respectively). TES false-positive results were significantly associated with parietal tumors and lateral patient positioning. Conclusions: Data support the use of mapping and combined monitoring via TES and DCS. The sole TES monitoring is reliable in most procedures but not in parietal tumors or those requiring lateral positioning. Although no indications are available in international guidelines, DCS should be recommended, particularly for cases approached by a lateral position.

Mirroring avatars: dissociation of action and intention in human motor resonance.

Observation of others' actions induces a subliminal activation of motor pathways (motor resonance) that is mediated by the mirror neuron system and reflects the motor program encoding the observed action. Whether motor resonance represents the movements composing an action or also its motor intention remains of debate, as natural actions implicitly contain their motor intentions. Here, action and intention are dissociated using a natural and an impossible action with the same grasping intention: subjects observe an avatar grasping a ball using either a natural hand action ('palmar' finger flexion) or an impossible hand action ('dorsal' finger flexion). Motor-evoked potentials (MEPs), elicited by single transcranial magnetic stimulation of the hand area in the primary motor cortex, were used to measure the excitability modulation of motor pathways during observation of the two different hand actions. MEPs were recorded from the opponens pollicis (OP), abductor digiti minimi (ADM) and extensor carpi radialis (ECR) muscles. A significant MEP facilitation was found in the OP, during observation of the grasping phase of the natural action; MEPs in the ADM were facilitated during observation of the hand opening phase of the natural action and of both opening and grasping phases of the impossible action. MEPs in the ECR were not affected. As different resonant responses are elicited by the observation of the two different actions, despite their identical intention, we conclude that the mirror neuron system cannot utilize the observer's subliminal motor program in the primary motor cortex to encode action intentions.

Negative motor responses to direct electrical stimulation: Behavioral assessment hides different effects on muscles.

A negative motor response (NMR) is defined as the inability to continue voluntary movements without losing consciousness when direct electrical stimulation (DES) is applied during awake neurosurgery. While visual inspection is most commonly used to define an NMR, the actual effect of stimulation on muscle activity has been neglected by recent neurosurgical literature. We show that behavioral assessment of NMRs hides different site-dependent effects on muscles as revealed by electromyography (EMG), describing ten cases of brain tumor patients undergoing awake neurosurgery while performing a hand-object manipulation task. DES-induced NMRs were assessed behaviorally and related to the underlying electromyographic recording. Quantitative analysis of motor unit recruitment and regularity between phasic muscle contractions was computed. We show that similar NMRs classified based on behavioral criteria can be associated with suppression, increased recruitment or mixed effects on ongoing hand muscles. In some cases, suppression of hand muscle activity is associated with involuntary recruitment of muscles not involved in the task. Interestingly, stimulation of behaviorally defined "negative areas" across the frontal and parietal lobes elicits different electromyographic patterns, depending on the stimulation site. This study provides novel preliminary background as to the heterogeneous profile of muscle activity during NMRs. In fact, EMG monitoring paired with behavioral assessment can distinguish between NMRs that, despite similarity on behavioral inspection, are different in their related EMG, possibly underlying different neural substrates. The identification of different circuits hidden in similar NMRs may become relevant when planning the extension of resection.

Clinical Pearls and Methods for Intraoperative Motor Mapping.

Resection of brain tumors involving motor areas and pathways requires the identification and preservation of various cortical and subcortical structures involved in motor control at the time of the procedure, in order to maintain the patient's full motor capacities. The use of brain mapping techniques has now been integrated into clinical practice for many years, as they help the surgeon to identify the neural structures involved in motor functions. A common definition of motor function, as well as knowledge of its neural organization, has been continuously evolving, underlining the need for implementing intraoperative strategies at the time of the procedure. Similarly, mapping strategies have been subjected to continuous changes, enhancing the likelihood of preservation of full motor capacities. As a general rule, the motor mapping strategy should be as flexible as possible and adapted strictly to the individual patient and clinical context of the tumor. In this work, we present an overview of current knowledge of motor organization, indications for motor mapping, available motor mapping, and monitoring strategies, as well as their advantages and limitations. The use of motor mapping improves resection and outcomes in patients harboring tumors involving motor areas and pathways, and should be considered the gold standard in the resection of this type of tumor.

Factors Influencing Mood Disorders and Health Related Quality of Life in Adults With Glioma: A Longitudinal Study.

OBJECTIVE: At present, it is not clear whether Mood Disorders (MD) and poor Health Related Quality of Life (HRQoL) in the glioma population correlate with features of the tumor, or rather with secondary symptoms associated with treatment. The aim of this study was to assess the prevalence of MD and decline in HRQoL in glioma patients, and to determine the main factors associated with these two variables. METHODS: 80 patients affected by lower-grade gliomas (LGGs) and 65 affected by high-grade gliomas (HGGs) were evaluated, from admission up to 12 months after surgery, for MD, HRQoL, clinical characteristics, and cognitive functions. Independent factors associated with MD and low HRQoL were identified by using bivariate analysis. RESULTS: Data showed that prevalence of low HRQoL was comparable in both groups during all the time points assessed (pre, 1, 3, 6 and 12 months after surgery). In contrast at 6 months following surgery, HGGs showed a higher prevalence of MD compared to LGGs;. Bivariate analysis revealed that factors associated with MD and HRQoL in LGGs and HGGs were different over the course of the disease. In LGGs, from the pre-operative period to one year post surgery, MD and low HRQOL were associated with the occurrence of cognitive deficits and, from the third month after surgery onward, they were also associated with the effect exerted by adjuvant treatments. In HGGs, MD were associated with cognitive deficits at 3 and 6 months after surgery, along with older age (65-75 years); HRQoL, in its Physical component in particular, was associated with older age only from 6 months after surgery. CONCLUSION: Factors associated with MD and low HRQoL were different in LGGs and HGGs over the course of the disease. In LGGs the effect of adjuvant treatments was prominent in determining the prevalence of both MD and poor HRQoL from the third month after surgery onward. In HGGs, MD and HRQoL were associated with age, at 3 and 6 months after surgery. In both, the occurrence of cognitive deficits was significantly associated with MD.

Targeting Primary Motor Cortex (M1) Functional Components in M1 Gliomas Enhances Safe Resection and Reveals M1 Plasticity Potentials.

Primary-Motor-Cortex (M1) hosts two functional components, at its posterior and anterior borders, being the first faster and more excitable. We developed a mapping-technique for M1 components identification and determined their functional cortical-subcortical architecture in M1 gliomas and the impact of their identification on tumor resection and motor performance. A novel advanced mapping technique was used in 102 tumors within M1 or CorticoSpinal-Tract to identify M1-two components. High-Frequency-stimulation (2-5 pulses) with an on-line qualitative and quantitative analysis of motor responses was used; the two components' cortical/subcortical spatial distribution correlated to clinical, tumor-related factor and patients' motor outcome; a cohort treated with standard-mapping was used for comparison. The two functional components were always identified on-line; in tumors not affecting M1, its functional segregation was preserved. In M1 tumors, two architectures, both preserving the two components, were disclosed: in 50%, a normal cortical/subcortical architecture emerged, while 50% revealed a distorted architecture with loss of anatomical reference and somatotopy, not associated with tumor histo-molecular features or volume, but with a previous treatment. Motor performance was maintained, suggesting functional compensation. By preserving the highest and resecting the lowest excitability component, the complete-resection increased with low morbidity. The real-time identification of two M1 functional components and the preservation of the highest excitability one increases safe resection, revealing M1 plasticity potentials.

The shape of motor resonance: right- or left-handed?

The human mirror neuron system is a fronto-parietal neural pathway which, when activated by action observation, gives rise to an internal simulation of the observed action (motor resonance). Here we demonstrate how handedness shapes the resonant response, by engaging right-handed (RH) and left-handed (LH) subjects in observation and execution of actions preferentially performed by the dominant hand. We hypothesize that since motor resonance reproduces subliminally the specific motor program for the observed action, it should be subject to motor constraints, such as handedness. A conjunction analysis for observed and executed actions revealed that handedness determines a lateralized activation of the areas engaged in motor resonance. Premotor-BA6 and parietal-BA40 are strongly left lateralized in RH subjects observing or moving their right hand, and to a lesser degree their left hand. Extremely LH subjects show a similar pattern of lateralization on the right, while more ambidextrous LH subjects show a more bilateral activation. The activation of a cortical network outside the mirror neuron system is also discussed.

Reproducing macaque lateral grasping and oculomotor networks using resting state functional connectivity and diffusion tractography.

Cortico-cortical networks involved in motor control have been well defined in the macaque using a range of invasive techniques. The advent of neuroimaging has enabled non-invasive study of these large-scale functionally specialized networks in the human brain; however, assessing its accuracy in reproducing genuine anatomy is more challenging. We set out to assess the similarities and differences between connections of macaque motor control networks defined using axonal tracing and those reproduced using structural and functional connectivity techniques. We processed a cohort of macaques scanned in vivo that were made available by the open access PRIME-DE resource, to evaluate connectivity using diffusion imaging tractography and resting state functional connectivity (rs-FC). Sectors of the lateral grasping and exploratory oculomotor networks were defined anatomically on structural images, and connections were reproduced using different structural and functional approaches (probabilistic and deterministic whole-brain and seed-based tractography; group template and native space functional connectivity analysis). The results showed that parieto-frontal connections were best reproduced using both structural and functional connectivity techniques. Tractography showed lower sensitivity but better specificity in reproducing connections identified by tracer data. Functional connectivity analysis performed in native space had higher sensitivity but lower specificity and was better at identifying connections between intrasulcal ROIs than group-level analysis. Connections of AIP were most consistently reproduced, although those connected with prefrontal sectors were not identified. We finally compared diffusion MR modelling with histology based on an injection in AIP and speculate on anatomical bases for the observed false negatives. Our results highlight the utility of precise ex vivo techniques to support the accuracy of neuroimaging in reproducing connections, which is relevant also for human studies.

Direct electrical stimulation of the premotor cortex shuts down awareness of voluntary actions.

A challenge for neuroscience is to understand the conscious and unconscious processes underlying construction of willed actions. We investigated the neural substrate of human motor awareness during awake brain surgery. In a first experiment, awake patients performed a voluntary hand motor task and verbally monitored their real-time performance, while different brain areas were transiently impaired by direct electrical stimulation (DES). In a second experiment, awake patients retrospectively reported their motor performance after DES. Based on anatomo-clinical evidence from motor awareness disorders following brain damage, the premotor cortex (PMC) was selected as a target area and the primary somatosensory cortex (S1) as a control area. In both experiments, DES on both PMC and S1 interrupted movement execution, but only DES on PMC dramatically altered the patients' motor awareness, making them unconscious of the motor arrest. These findings endorse PMC as a crucial hub in the anatomo-functional network of human motor awareness.