A revision of the dorsal origin of the frontal aslant tract (FAT) in the superior frontal gyrus: a DWI-tractographic study.

The frontal aslant tract (FAT) is a white matter tract connecting the superior frontal gyrus (SFG) to the inferior frontal gyrus (IFG). Its dorsal origin is identified in humans in the medial wall of the SFG, in the supplementary motor complex (SM-complex). However, empirical observation shows that many FAT fibres appear to originate from the dorsal, rather than medial, portion of the SFG. We quantitatively investigated the actual origin of FAT fibres in the SFG, specifically discriminating between terminations in the medial wall and in the convexity of the SFG. We analysed data from 105 subjects obtained from the Human Connectome Project (HCP) database. We parcelled the cortex of the IFG, dorsal SFG and medial SFG in several regions of interest (ROIs) ordered in a caudal-rostral direction, which served as seed locations for the generation of streamlines. Diffusion imaging data (DWI) was processed using a multi-shell multi-tissue CSD-based algorithm. Results showed that the number of streamlines originating from the dorsal wall of the SFG significantly exceeds those from the medial wall of the SFG. Connectivity patterns between ROIs indicated that FAT sub-bundles are segregated in parallel circuits ordered in a caudal-rostral direction. Such high degree of coherence in the streamline trajectory allows to establish pairs of homologous cortical parcels in the SFG and IFG. We conclude that the frontal origin of the FAT is found in both dorsal and medial surfaces of the superior frontal gyrus.

Connectivity by the Frontal Aslant Tract (FAT) Explains Local Functional Specialization of the Superior and Inferior Frontal Gyri in Humans When Choosing Predictive over Reactive Strategies: A Tractography-Guided TMS Study.

Predictive and reactive behaviors represent two mutually exclusive strategies in a sensorimotor task. Predictive behavior consists in internally estimating timing and features of a target stimulus and relies on a cortical medial frontal system [superior frontal gyrus (SFG)]. Reactive behavior consists in waiting for actual perception of the target stimulus and relies on the lateral frontal cortex [inferior frontal gyrus (IFG)]. We investigated whether SFG-IFG connections by the frontal aslant tract (FAT) can mediate predictive/reactive interactions. In 19 healthy human volunteers, we applied online transcranial magnetic stimulation (TMS) to six spots along the medial and lateral terminations of the FAT, during the set period of a delayed reaction task. Such scenario can be solved using either predictive or reactive strategies. TMS increased the propensity toward reactive behavior if applied to a specific portion of the IFG and increased predictive behavior when applied to a specific SFG spot. The two active spots in the SFG and IFG were directly connected by a sub-bundle of FAT fibers as indicated by diffusion-weighted imaging (DWI) tractography. Since FAT connectivity identifies two distant cortical nodes with opposite functions, we propose that the FAT mediates mutually inhibitory interactions between SFG and IFG to implement a "winner takes all" decisional process. We hypothesize such role of the FAT to be domain-general, whenever competition occurs between internal predictive and external reactive behaviors. Finally, we also show that anatomic connectivity is a powerful factor to explain and predict the spatial distribution of brain stimulation effects.SIGNIFICANCE STATEMENT We interact with sensory cues adopting two main mutually-exclusive strategies: (1) trying to anticipate the occurrence of the cue or (2) waiting for the GO-signal to be manifest and react to it. Here, we showed, by using noninvasive brain stimulation [transcranial magnetic stimulation (TMS)], that two specific cortical regions in the superior frontal gyrus (SFG) and the inferior frontal gyrus (IFG) have opposite roles in facilitating a predictive or a reactive strategy. Importantly these two very distant regions but with highly interconnected functions are specifically connected by a small white matter bundle, which mediates the direct competition and exclusiveness between predictive and reactive strategies. More generally, implementing anatomic connectivity in TMS studies strongly reduces spatial noise.

Functional Approaches to the Surgery of Brain Gliomas.

In the surgery of gliomas, recent years have witnessed unprecedented theoretical and technical development, which extensively increased indication to surgery. On one hand, it has been solidly demonstrated the impact of gross total resection on life expectancy. On the other hand, the paradigm shift from classical cortical localization of brain function towards connectomics caused by the resurgence of awake surgery and the advent of tractography has permitted safer surgeries focused on subcortical white matter tracts preservation and allowed for surgical resections within regions, such as Broca's area or the primary motor cortex, which were previously deemed inoperable. Furthermore, new asleep electrophysiological techniques have been developed whenever awake surgery is not an option, such as operating in situations of poor compliance (including paediatric patients) or pre-existing neurological deficits. One such strategy is the use of intraoperative neurophysiological monitoring (IONM), enabling the identification and preservation of functionally defined, but anatomically ambiguous, cortico-subcortical structures through mapping and monitoring techniques. These advances tie in with novel challenges, specifically risk prediction and the impact of neuroplasticity, the indication for tumour resection beyond visible borders, or supratotal resection, and most of all, a reappraisal of the importance of the right hemisphere from early psychosurgery to mapping and preservation of social behaviour, executive control, and decision making.Here we review current advances and future perspectives in a functional approach to glioma surgery.

How to Test the Association Between Baseline Performance Level and the Modulatory Effects of Non-Invasive Brain Stimulation Techniques.

Behavioral effects of non-invasive brain stimulation techniques (NIBS) can dramatically change as a function of different factors (e.g., stimulation intensity, timing of stimulation). In this framework, lately there has been a growing interest toward the importance of considering the inter-individual differences in baseline performance and how they are related with behavioral NIBS effects. However, assessing how baseline performance level is associated with behavioral effects of brain stimulation techniques raises up crucial methodological issues. How can we test whether the performance at baseline is predictive of the effects of NIBS, when NIBS effects themselves are estimated with reference to baseline performance? In this perspective article, we discuss the limitations connected to widely used strategies for the analysis of the association between baseline value and NIBS effects, and review solutions to properly address this type of question.

Action planning modulates the representation of object features in human fronto-parietal and occipital cortex.

The visual cortex has been extensively studied to investigate its role in object recognition but to a lesser degree to determine how action planning influences the representation of objects' features. We used functional MRI and pattern classification methods to determine if during action planning, object features (orientation and location) could be decoded in an action-dependent way. Sixteen human participants used their right dominant hand to perform movements (Align or Open reach) towards one of two 3D-real oriented objects that were simultaneously presented and placed on either side of a fixation cross. While both movements required aiming towards target location, Align but not Open reach movements required participants to precisely adjust hand orientation. Therefore, we hypothesized that if the representation of object features is modulated by the upcoming action, pre-movement activity pattern would allow more accurate dissociation between object features in Align than Open reach tasks. We found such dissociation in the anterior and posterior parietal cortex, as well as in the dorsal premotor cortex, suggesting that visuomotor processing is modulated by the upcoming task. The early visual cortex showed significant decoding accuracy for the dissociation between object features in the Align but not Open reach task. However, there was no significant difference between the decoding accuracy in the two tasks. These results demonstrate that movement-specific preparatory signals modulate object representation in the frontal and parietal cortex, and to a lesser extent in the early visual cortex, likely through feedback functional connections.

Stimulation of Different Sectors of the Human Dorsal Premotor Cortex Induces a Shift from Reactive to Predictive Action Strategies and Changes in Motor Inhibition: A Dense Transcranial Magnetic Stimulation (TMS) Mapping Study.

Delayed motor tasks require timely interaction between immobility and action. The neural substrates of these processes probably reside in the premotor and motor circuits; however, fine-grained anatomical/functional information is still lacking. Participants performed a delayed simple reaction task, structured as a ready-set-go sequence, with a fixed, predictable, SET-period. Responses were given with lip movements. During the SET-period, we performed a systematic dense-mapping of the bilateral dorsal premotor region (dPM) by means of single transcranial magnetic stimulation (TMS) pulses on an 18-spot mapping grid, interleaved with sham TMS which served as a baseline. Reaction times (RTs) in TMS trials over each grid spot were compared to RTs in sham trials to build a statistical parametric z-map. The results reveal a rostro-caudal functional gradient in the dPM. TMS of the rostral dPM induced a shift from reactive towards predictive response strategies. TMS of the caudal dPM interfered with the SET-period duration. By means of dense TMS mapping, we have drawn a putative functional map of the role of the dPM during the SET-period. A higher-order rostral component is involved in setting action strategies and a caudal, lower-order, part is probably involved in the inhibitory control of motor output.

Feasibility of cerebello-cortical stimulation for intraoperative neurophysiological monitoring of cerebellar mutism.

BACKGROUND: Cerebellar mutism can occur in a third of children undergoing cerebellar resections. Recent evidence proposes it may arise from uni- or bilateral damage of cerebellar efferents to the cortex along the cerebello-dento-thalamo-cortical pathway. At present, no neurophysiological procedure is available to monitor this pathway intraoperatively. Here, we specifically aimed at filling this gap. METHODS: We assessed 10 patients undergoing posterior fossa surgery using a conditioning-test stimulus paradigm. Electrical conditioning stimuli (cStim) were delivered to the exposed cerebellar cortex at interstimulus intervals (ISIs) of 8-24 ms prior to transcranial electric stimulation of the motor cortex, which served as test stimulus (tStim). The variation of motor-evoked potentials (MEP) to cStim + tStim compared with tStim alone was taken as a measure of cerebello-cortical connectivity. RESULTS: cStim alone did not produce any MEP. cStim preceding tStim produced a significant inhibition at 8 ms (p < 0.0001) compared with other ISIs when applied to the lobules IV-V-VI in the anterior cerebellum and the lobule VIIB in the posterior cerebellum. Mixed effects of decrease and increase in MEP amplitude were observed in these areas for longer ISIs. CONCLUSIONS: The inhibition exerted by cStim at 8 ms on the motor cortex excitability is likely to be the product of activity along the cerebello-dento-thalamo-cortical pathway. We show that monitoring efferent cerebellar pathways to the motor cortex is feasible in intraoperative settings. This study has promising implications for pediatric posterior fossa surgery with the aim to preserve the cerebello-cortical pathways and thus prevent cerebellar mutism.

Long-term motor deficit in brain tumour surgery with preserved intra-operative motor-evoked potentials.

Muscle motor-evoked potentials are commonly monitored during brain tumour surgery in motor areas, as these are assumed to reflect the integrity of descending motor pathways, including the corticospinal tract. However, while the loss of muscle motor-evoked potentials at the end of surgery is associated with long-term motor deficits (muscle motor-evoked potential-related deficits), there is increasing evidence that motor deficit can occur despite no change in muscle motor-evoked potentials (muscle motor-evoked potential-unrelated deficits), particularly after surgery of non-primary regions involved in motor control. In this study, we aimed to investigate the incidence of muscle motor-evoked potential-unrelated deficits and to identify the associated brain regions. We retrospectively reviewed 125 consecutive patients who underwent surgery for peri-Rolandic lesions using intra-operative neurophysiological monitoring. Intraoperative changes in muscle motor-evoked potentials were correlated with motor outcome, assessed by the Medical Research Council scale. We performed voxel-lesion-symptom mapping to identify which resected regions were associated with short- and long-term muscle motor-evoked potential-associated motor deficits. Muscle motor-evoked potentials reductions significantly predicted long-term motor deficits. However, in more than half of the patients who experienced long-term deficits (12/22 patients), no muscle motor-evoked potential reduction was reported during surgery. Lesion analysis showed that muscle motor-evoked potential-related long-term motor deficits were associated with direct or ischaemic damage to the corticospinal tract, whereas muscle motor-evoked potential-unrelated deficits occurred when supplementary motor areas were resected in conjunction with dorsal premotor regions and the anterior cingulate. Our results indicate that long-term motor deficits unrelated to the corticospinal tract can occur more often than currently reported. As these deficits cannot be predicted by muscle motor-evoked potentials, a combination of awake and/or novel asleep techniques other than muscle motor-evoked potentials monitoring should be implemented.

Thematic Reanalysis in the Left Posterior Parietal Sulcus: A TMS Study.

Understanding who does what to whom is at the core of sentence comprehension. The actors that contribute to the verb meaning are labeled thematic roles. We used transcranial magnetic stimulation (TMS) to verify the possible impact of verb semantics on the thematic role encoding process that has been shown to involve the posterior portion of the left posterior parietal sulcus (PPS; Finocchiaro et al., 2015). Sixteen participants underwent TMS and sham stimulation sessions while performing an agent-decision task, in which they had to decide by key press which of the two arguments was the agent of visually presented sentences or pseudo-sentences. The (pseudo)sentences were all reversible and were presented in the active or passive diathesis. Double pulse TMS was delivered to the posterior part of the intraparietal sulcus in an event-related fashion, at two different time windows: 200-400 ms (T1) or 600-800 ms (T2) time-locked to the presentation of the (pseudo)sentence. Results showed that TMS increased accuracy on passive sentences and pseudo-sentences as compared to active sentences and to the baseline, sham condition. Indeed, the presence of a verb with a full semantic representation was not a necessary precondition for the TMS-induced facilitation of passive (pseudo)sentences. Stimulation timing had no effect on accuracy for sentences vs. pseudo-sentences. These observations support the idea that the posterior parietal site is recruited when the correct interpretation of a sentence requires reanalysis of temporarily encoded thematic roles (as in reversible passive sentences) even when the verb is not an entry in the lexicon and hence does not have a semantic representation. Results are consistent with previous evidence and deserve further investigation in larger experimental samples. Increasing the number and variety of stimulus sentences, and administering TMS to additional control sites will be key to further articulate the conclusions allowed by these initial findings.

Modulating the influence of recent trial history on attentional capture via transcranial magnetic stimulation (TMS) of right TPJ.

In visual search, salient yet task-irrelevant distractors in the stimulus array interfere with target selection. This is due to the unwanted shift of attention towards the salient stimulus-the so-called attentional capture effect, which delays deployment of attention onto the target. Although powerful and automatic, attentional capture by a salient distractor is nonetheless antagonized by distractor-filtering mechanisms and is further modulated by cross-trial contingencies: The distractor cost is typically more robust when no distraction has been experienced in the immediate past, compared to when a distractor was present on the immediately preceding trial. Here, we used transcranial magnetic stimulation (TMS) to shed light on the causal role of two crucial nodes of the ventral attention network, namely the Temporo-Parietal Junction (TPJ) and the Middle Frontal Gyrus (MFG), in the exogenous control of attention (i.e., attentional capture) and its history-dependent modulation. Participants were asked to discriminate the direction of a target arrow while ignoring a task-irrelevant salient distractor, when present. Immediately after display onset, 10 Hz triple-pulse TMS was delivered either to TPJ or MFG on the right hemisphere. Results demonstrated that stimulation of right TPJ-but not of right MFG, strongly modulated attentional capture as a function of the type of previous trial, by somewhat enhancing the distractor-related cost when the preceding trial was a distractor-absent trial and significantly decreasing the cost when the preceding trial was a distractor-present trial. These findings indicate that TMS of right TPJ exacerbates the effect of the recent history, likely reflecting enhanced updating of the predictive model that dynamically governs proactive distractor-filtering mechanisms. More generally, the results attest to a role of TPJ in mediating the history-dependent modulation of attentional capture.

Gaze direction influences grasping actions towards unseen, haptically explored, objects.

Haptic exploration produces mental object representations that can be memorized for subsequent object-directed behaviour. Storage of haptically-acquired object images (HOIs), engages, besides canonical somatosensory areas, the early visual cortex (EVC). Clear evidence for a causal contribution of EVC to HOI representation is still lacking. The use of visual information by the grasping system undergoes necessarily a frame of reference shift by integrating eye-position. We hypothesize that if the motor system uses HOIs stored in a retinotopic coding in the visual cortex, then its use is likely to depend at least in part on eye position. We measured the kinematics of 4 fingers in the right hand of 15 healthy participants during the task of grasping different unseen objects behind an opaque panel, that had been previously explored haptically. The participants never saw the object and operated exclusively based on haptic information. The position of the object was fixed, in front of the participant, but the subject's gaze varied from trial to trial between 3 possible positions, towards the unseen object or away from it, on either side. Results showed that the middle and little fingers' kinematics during reaching for the unseen object changed significantly according to gaze position. In a control experiment we showed that intransitive hand movements were not modulated by gaze direction. Manipulating eye-position produces small but significant configuration errors, (behavioural errors due to shifts in frame of reference) possibly related to an eye-centered frame of reference, despite the absence of visual information, indicating sharing of resources between the haptic and the visual/oculomotor system to delayed haptic grasping.

The role of the l-IPS in the comprehension of reversible and irreversible sentences: an rTMS study.

Thematic roles can be seen as semantic labels assigned to who/what is taking part in the event denoted by a verb. Encoding thematic relations is crucial for sentence interpretation since it relies on both syntactic and semantic aspects. In previous studies, repetitive transcranial magnetic stimulation (rTMS) over the left inferior intraparietal sulcus (l-IPS) selectively influenced performance accuracy on reversible passive (but not active) sentences. The effect was attributed to the fact that in these sentences the assignment of the agent and theme roles requires re-analysis of the first-pass sentence parsing. To evaluate the role of reversibility and non-canonical word order (passive voice) on the effect, rTMS was applied over l-IPS during a sentence comprehension task that included reversible and irreversible, active and passive sentences. Participants were asked to identify who/what was performing the action or who/what the action was being performed on. Stimulation of the l-IPS increased response time on reversible passive sentences but not on reversible active sentences. Importantly, no effect was found on irreversible sentences, irrespective of sentence diathesis.Results suggest that neither reversibility nor sentence diathesis alone are responsible for the effect and that the effect is likely to be triggered/constrained by a combination of semantic reversibility and non-canonical word order. Combined with the results of previous studies, and irrespective of the specific role of each feature, these findings support the view that the l-IPS is critically involved in the assignment of thematic roles in reversible sentences.

The Topography of Visually Guided Grasping in the Premotor Cortex: A Dense-Transcranial Magnetic Stimulation (TMS) Mapping Study.

Visuomotor transformations at the cortical level occur along a network where posterior parietal regions are connected to homologous premotor regions. Grasping-related activity is represented in a diffuse, ventral and dorsal system in the posterior parietal regions, but no systematic causal description of a premotor counterpart of a similar diffuse grasping representation is available. To fill this gap, we measured the kinematics of right finger movements in 17 male and female human participants during grasping of three objects of different sizes. Single-pulse transcranial magnetic stimulation was applied 100 ms after visual presentation of the object over a regular grid of 8 spots covering the left premotor cortex (PMC) and 2 Sham stimulations. Maximum finger aperture during reach was used as the feature to classify object size in different types of classifiers. Classification accuracy was taken as a measure of the efficiency of visuomotor transformations for grasping. Results showed that transcranial magnetic stimulation reduced classification accuracy compared with Sham stimulation when it was applied to 2 spots in the ventral PMC and 1 spot in the medial PMC, corresponding approximately to the ventral PMC and the dorsal portion of the supplementary motor area. Our results indicate a multifocal representation of object geometry for grasping in the PMC that matches the known multifocal parietal maps of grasping representations. Additionally, we confirm that, by applying a uniform spatial sampling procedure, transcranial magnetic stimulation can produce cortical functional maps independent of a priori spatial assumptions.SIGNIFICANCE STATEMENT Visually guided actions activate a large frontoparietal network. Here, we used a dense grid of transcranial magnetic stimulation spots covering the whole premotor cortex (PMC), to identify with accurate spatial mapping the functional specialization of the human PMC during grasping movement. Results corroborate previous findings about the role of the ventral PMC in preshaping the fingers according to the size of the target. Crucially, we found that the medial part of PMC, putatively covering the supplementary motor area, plays a direct role in object grasping. In concert with findings in nonhuman primates, these results indicate a multifocal representation of object geometry for grasping in the PMC and expand our understanding of how our brain integrates visual and motor information to perform visually guided actions.

Decoding motor imagery and action planning in the early visual cortex: Overlapping but distinct neural mechanisms.

Recent evidence points to a role of the primary visual cortex that goes beyond visual processing into high-level cognitive and motor-related functions, including action planning, even in absence of feedforward visual information. It has been proposed that, at the neural level, motor imagery is a simulation based on motor representations, and neuroimaging studies have shown overlapping and shared activity patterns for motor imagery and action execution in frontal and parietal cortices. Yet, the role of the early visual cortex in motor imagery remains unclear. Here we used multivoxel pattern analyses on functional magnetic resonance imaging (fMRI) data to examine whether the content of motor imagery and action intention can be reliably decoded from the activity patterns in the retinotopic location of the target object in the early visual cortex. Further, we investigated whether the discrimination between specific actions generalizes across imagined and intended movements. Eighteen right-handed human participants (11 females) imagined or performed delayed hand actions towards a centrally located object composed of a small shape attached on a large shape. Actions consisted of grasping the large or small shape, and reaching to the center of the object. We found that despite comparable fMRI signal amplitude for different planned and imagined movements, activity patterns in the early visual cortex, as well as dorsal premotor and anterior intraparietal cortex, accurately represented action plans and action imagery. However, movement content is similar irrespective of whether actions are actively planned or covertly imagined in parietal but not early visual or premotor cortex, suggesting a generalized motor representation only in regions that are highly specialized in object directed grasping actions and movement goals. In sum, action planning and imagery have overlapping but non identical neural mechanisms in the cortical action network.

Cortico-cortical connectivity between the superior and inferior parietal lobules and the motor cortex assessed by intraoperative dual cortical stimulation.

BACKGROUND: The function of the primate's posterior parietal cortex (PPC) in sensorimotor transformations is well-established, though in humans its complexity is still challenging. Well-established models indicate that the posterior parietal cortex influences motor output indirectly, by means of connections to the premotor cortex, which in turn is directly connected to the motor cortex. OBJECTIVE: The possibility that the PPC could be at the origin of direct afferents to M1 has been suggested in humans but has never been confirmed directly. We aim to do so in the present study by using the novel technique of paired intraoperative cortical stimulation. METHODS: In the present cross-sectional study, we assessed during intraoperative monitoring of the corticospinal tract in brain tumour patients the existence of short-latency effects of parietal stimulation on corticospinal excitability to the upper limb. MEPs were evoked by test stimuli over the motor cortex, which were preceded in some trials by conditioning stimuli on the PPC. RESULTS: We identified two active cortical loci. One in the inferior parietal lobule exerted short-latency excitatory effects and one in the superior parietal lobule that drove short-latency inhibitory effects on cortical motor output. All active foci were distributed in the rostral portion of the PPC and on the postcentral sulcus. CONCLUSIONS: For the first time in humans, the present data show direct evidence in favour of a distributed system of connections from the posterior parietal cortex to the ipsilateral primary motor cortex. In addition, we show that dual cortical stimulation is a novel and efficient technique to investigate intraoperative brain connectivity in the anaesthetized patient.

Two Distinct Systems Represent Contralateral and Ipsilateral Sensorimotor Processes in the Human Premotor Cortex: A Dense TMS Mapping Study.

Animal brains contain behaviorally committed representations of the surrounding world, which integrate sensory and motor information. In primates, sensorimotor mechanisms reside in part in the premotor cortex (PM), where sensorimotor neurons are topographically clustered according to functional specialization. Detailed functional cartography of the human PM is still under investigation. We explored the topographic distribution of spatially dependent sensorimotor functions in healthy volunteers performing left or right, hand or foot, responses to visual cues presented in the left or right hemispace, thus combining independently stimulus side, effector side, and effector type. Event-related transcranial magnetic stimulation was applied to single spots of a dense grid of 10 points on the participants' left hemiscalp, covering the whole PM. Results showed: (1) spatially segregated hand and foot representations, (2) focal representations of contralateral cues and movements in the dorsal PM, and (3) distributed representations of ipsilateral cues and movements in the ventral and dorso-medial PM. The present novel causal information indicates that (1) the human PM is somatotopically organized and (2) the left PM contains sensory-motor representations of both hemispaces and of both hemibodies, but the hemispace and hemibody contralateral to the PM are mapped on a distinct, nonoverlapping cortical region compared to the ipsilateral ones.