The auditory stimulus reduced the visual inhibition of return: Evidence from psychophysiological interaction analysis.

Visual inhibition of return (IOR) is a mechanism for preventing attention from returning to previously examined spatial locations. Previous studies have found that auditory stimuli presented simultaneously with a visual target can reduce or even eliminate the visual IOR. However, the mechanism responsible for decreased visual IOR accompanied by auditory stimuli is unclear. Using functional magnetic resonance imaging, we aimed to investigate how auditory stimuli reduce visual IOR. Behaviorally, we found that the visual IOR accompanying auditory stimuli was significant but smaller than the visual IOR. Neurally, only in the validly cued trials, the superior temporal gyrus showed increased neural coupling with the intraparietal sulcus, presupplementary motor area, and some other areas in audiovisual conditions compared with visual conditions. These results suggest that the reduction in visual IOR by the simultaneous auditory stimuli may be due to a dual mechanism: rescuing the suppressed visual salience and facilitating response initiation. Our results support crossmodal interactions can occur across multiple neural levels and cognitive processing stages. This study provides a new perspective for understanding attention-orienting networks and response initiation based on crossmodal information.

Audio and visual speech emotion activate the left pre-supplementary motor area.

Sensorimotor brain areas have been implicated in the recognition of emotion expressed on the face and through nonverbal vocalizations. However, no previous study has assessed whether sensorimotor cortices are recruited during the perception of emotion in speech-a signal that includes both audio (speech sounds) and visual (facial speech movements) components. To address this gap in the literature, we recruited 24 participants to listen to speech clips produced in a way that was either happy, sad, or neutral in expression. These stimuli also were presented in one of three modalities: audio-only (hearing the voice but not seeing the face), video-only (seeing the face but not hearing the voice), or audiovisual. Brain activity was recorded using electroencephalography, subjected to independent component analysis, and source-localized. We found that the left presupplementary motor area was more active in response to happy and sad stimuli than neutral stimuli, as indexed by greater mu event-related desynchronization. This effect did not differ by the sensory modality of the stimuli. Activity levels in other sensorimotor brain areas did not differ by emotion, although they were greatest in response to visual-only and audiovisual stimuli. One possible explanation for the pre-SMA result is that this brain area may actively support speech emotion recognition by using our extensive experience expressing emotion to generate sensory predictions that in turn guide our perception.

A Practical Approach to Imaging of the Supplementary Motor Area and Its Subcortical Connections.

PURPOSE OF REVIEW: First, an anatomical and functional review of these cortical areas and subcortical connections with T-fMRI and tractography techniques; second, to demonstrate the value of this approach in neurosurgical planning in a series of patients with tumors close to the SMA. RECENT FINDINGS: Implications in language and cognitive networks with a clear hemispheric lateralization of these SMA/pre-SMA. The recommendation of the use of the advanced neuroimaging studies for surgical planning and preservation of these areas. The SMA/pre-SMA and their subcortical connections are functional areas to be taken into consideration in neurosurgical planning. These areas would be involved in the control/inhibition of movement, in verbal expression and fluency and in tasks of cognitive control capacity. Its preservation is key to the patient's postsurgical cognitive and functional evolution.

Identifying the neural correlates of doorway freezing in Parkinson's disease.

Freezing of gait (FOG) in Parkinson's disease (PD) is frequently triggered upon passing through narrow spaces such as doorways. However, despite being common the neural mechanisms underlying this phenomenon are poorly understood. In our study, 19 patients who routinely experience FOG performed a previously validated virtual reality (VR) gait paradigm where they used foot-pedals to navigate a series of doorways. Patients underwent testing randomised between both their "ON" and "OFF" medication states. Task performance in conjunction with blood oxygenation level dependent (BOLD) signal changes between "ON" and "OFF" states were compared within each patient. Specifically, as they passed through a doorway in the VR environment patients demonstrated significantly longer "footstep" latencies in the OFF state compared to the ON state. As seen clinically in FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. Functional magnetic resonance imaging revealed that footstep prolongation on passing through doorways was associated with selective hypoactivation in the presupplementary motor area (pSMA) bilaterally. Task-based functional connectivity analyses revealed that increased latency in response to doorways was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN. These findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the "hyperdirect" pathway in the generation of this phenomenon.

Probing the Cognitive Mechanism of Mental Representational Change During Chunk Decomposition: A Parametric fMRI Study.

Chunk decomposition plays an important role in cognitive flexibility in particular with regards to representational change, which is critical for insight problem solving and creative thinking. In this study, we investigated the cognitive mechanism of decomposing Chinese character chunks through a parametric fMRI design. Our results from this parametric manipulation revealed widely distributed activations in frontal, parietal, and occipital cortex and negative activations in parietal and visual areas in response to chunk tightness during decomposition. To mentally manipulate the element of a given old chunk, superior parietal lobe appears to support element restructuring in a goal-directed way, whereas the negatively activated inferior parietal lobe may support preventing irrelevant objects from being attended. Moreover, determining alternative ways of restructuring requires a constellation of frontal areas in the cognitive control network, such as the right lateral prefrontal cortex in inhibiting the predominant chunk representations, the presupplementary motor area in initiating a transition of mental task set, and the inferior frontal junction in establishing task sets. In conclusion, this suggests that chunk decomposition reflects mental transformation of problem representation from an inappropriate state to a new one alongside with an evaluation of novel and insightful solutions by the caudate in the dorsal striatum.

The prefrontal cortex achieves inhibitory control by facilitating subcortical motor pathway connectivity.

Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control.

Dissociable roles of preSMA in motor sequence chunking and hand switching-a TMS study.

Motor chunking, the grouping of individual movements into larger units, is crucial for sequential motor performance. The presupplementary motor area (preSMA) is involved in chunking and other related processes such as task switching, response selection, and response inhibition that are crucial for organizing sequential movements. However, previous studies have not systematically differentiated the role of preSMA in motor chunking and hand switching, thus leaving its relative contribution to each of these processes unclear. The aim of this study is to demonstrate the differential role of preSMA in motor chunking and hand switching. We designed motor sequences in which different kinds of hand switches (switching toward the right or left hand or continuing with the right hand) were counterbalanced across between- and within-chunk sequence points. Eighteen healthy, right-handed participants practiced four short subsequences (chunks) of key presses. In a subsequent task, these chunks had to be concatenated into one long sequence. We applied double-pulse transcranial magnetic stimulation (TMS) over left preSMA or left M1 areas at sequence initiation, between chunks, or within chunks. TMS over the left preSMA significantly slowed the next response when stimulation was given between chunks, but only if a hand switch toward the contralateral (right) hand was required. PreSMA stimulation within chunks did not interfere with responses. TMS over the left M1 area delayed responses with the contralateral hand, both within and between chunks. Both preSMA and M1 stimulation decreased response times at sequence initiation. These results suggest that left preSMA is not necessary for chunking per se, but rather for organizing complex movements that require chunking and hand switching simultaneously.

Expectations and violations: delineating the neural network of proactive inhibitory control.

The ability to stop a prepared response (reactive inhibition) appears to depend on the degree to which stopping is expected (proactive inhibition). Functional MRI studies have shown that activation during proactive and reactive inhibition overlaps, suggesting that the whole neural network for reactive inhibition becomes already activated in anticipation of stopping. However, these studies measured proactive inhibition as the effect of stop-signal probability on activation during go trials. Therefore, activation could reflect expectation of a stop-signal (evoked by the stop-signal probability cue), but also violation of this expectation because stop-signals do not occur on go trials. We addressed this problem, using a stop-signal task in which the stop-signal probability cue and the go-signal were separated in time. Hence, we could separate activation during the cue, reflecting expectation of the stop-signal, from activation during the go-signal, reflecting expectation of the stop-signal or violation of that expectation. During the cue, the striatum, the supplementary motor complex (SMC), and the midbrain activated. During the go-signal, the right inferior parietal cortex (IPC) and the right inferior frontal cortex (IFC) activated. These findings suggest that the neural network previously associated with proactive inhibition can be subdivided into two components. One component, including the striatum, the SMC, and the midbrain, activated during the cue, implicating this network in proactive inhibition. Another component, consisting of the right IPC and the right IFC, activated during the go-signal. Rather than being involved in proactive inhibition, this network appears to be involved in processes associated with violation of expectations.

Distinct neural representations of hand movement direction between motor imagery and execution in the presupplementary motor area.

Motor simulation theory proposes a functional equivalence between motor execution (ME) and its simulation, suggesting that motor imagery (MI) is the self-intentioned simulation of one's actions. This study used functional magnetic resonance imaging (fMRI) with multivoxel pattern analysis to test whether the direction of hand movement is represented with a similar neural code between ME and MI. In our study, participants used their right hand to move an on-screen cursor in the left-right direction with a joystick or imagined the same movement without execution. The results indicated that the left-right direction as well as their modality (ME or MI) could be decoded significantly above the chance level in the presupplementary motor area (pre-SMA) and primary visual cortex (V1). Next, we used activation patterns of ME as inputs to the decoder to predict hand move directions in MI sessions and found a significantly higher-than-chance accuracy only in V1, not in pre-SMA. Moreover, the representational similarity analysis showed similar activation patterns for the same directions between ME and MI in V1 but not in pre-SMA. This study's finding indicates distinct spatial activation patterns for movement directions between ME and MI in pre-SMA.

The Effect of Coil Orientation on the Stimulation of the Pre-Supplementary Motor Area: A Combined TMS and EEG Study.

Studies using transcranial magnetic stimulation (TMS) have demonstrated the importance of direction and intensity of the applied current when the primary motor cortex (M1) is targeted. By varying these, it is possible to stimulate different subsets of neural elements, as demonstrated by modulation of motor evoked potentials (MEPs) and motor behaviour. The latter involves premotor areas as well, and among them, the presupplementary motor area (pre-SMA) has recently received significant attention in the study of motor inhibition. It is possible that, similar to M1, different neuronal populations can be activated by varying the direction and intensity of TMS; however, the absence of a direct electrophysiological outcome has limited this investigation. The problem can be solved by quantifying direct cortical responses by means of combined TMS and electroencephalography (TMS-EEG). We investigated the effect of variable coil orientations (0°, 90°, 180° and 270°) and stimulation intensities (100%, 120% and 140% of resting motor threshold) on local mean field potential (LMFP), transcranial evoked potential (TEP) peaks and TMS-related spectral perturbation (TRSP) from pre-SMA stimulation. As a result, early and late LMFP and peaks were larger, with the coil handle pointing posteriorly (0°) and laterally (90°). This was true also for TRSP in the ß-γ range, but, surprisingly, θ-α TRSP was larger with the coil pointing at 180°. A 90° orientation activated the right M1, as shown by MEPs elicitation, thus limiting the spatial specificity of the stimulation. These results suggest that coil orientation and stimulation intensity are critical when stimulating the pre-SMA.

Non-invasive brain stimulation modulates neural correlates of performance monitoring in patients with obsessive-compulsive disorder.

Overactive performance monitoring, as reflected by enhanced neural responses to errors (the error-related negativity, ERN), is considered a biomarker for obsessive-compulsive disorder (OCD) and may be a promising target for novel treatment approaches. Prior research suggests that non-invasive brain stimulation with transcranial direct current stimulation (tDCS) may reduce the ERN in healthy individuals, yet no study has investigated its efficacy in attenuating the ERN in OCD. In this preregistered, randomized, sham-controlled, crossover study, we investigated effects of tDCS on performance monitoring in patients with OCD (n = 28) and healthy individuals (n = 28). Cathodal and sham tDCS was applied over the presupplementary motor area (pre-SMA) in two sessions, each followed by electroencephalogram recording during a flanker task. Cathodal tDCS reduced the ERN amplitude compared to sham tDCS, albeit this effect was only marginally significant (p = .052; mean difference: 0.86 µV). Additionally, cathodal tDCS reduced the correct-response negativity and increased the error positivity. These neural modulations were not accompanied by behavioral changes. Moreover, we found no evidence that the tDCS effect was more pronounced in the patient group. In summary, our findings indicate that tDCS over the pre-SMA modulates neural correlates of performance monitoring across groups. Therefore, this study represents a valuable starting point for future research to determine whether repeated tDCS application induces a more pronounced ERN attenuation and normalizes aberrant performance monitoring in the long term, thereby potentially alleviating obsessive-compulsive symptoms and providing a psychophysiological intervention strategy for individuals who do not benefit sufficiently from existing interventions.

Neuronal Representations of Tactic-Based Sensorimotor Transformations in the Primate Medial Prefrontal, Presupplementary, and Supplementary Motor Areas: A Comparative Study.

Adaptive context-dependent behaviors necessitate the flexible selection of multiple behavioral tactics, i.e., internal protocols for selecting an action. Previous primate studies have shown that the posterior medial prefrontal cortex (pmPFC) contributes to the selection, retention, and use of tactics, but the manner in which this area employs selected tactics to convert sensory information into action and how that manner differs from downstream cortical motor areas have yet to be fully elucidated. To address this issue, the present study recorded neuronal activity in two monkeys as they performed a two-choice arm reaching task that required the selection of multiple tactics when converting spatial cue information into the direction of arm reaching. Neuronal populations in both pmPFC and presupplementary motor area (pre-SMA) represented tactics during their selection, maintenance in memory, and their use in determining an action. Additionally, they represented the monkeys' action in the behavioral epoch in which the direction of reaching was determined. A striking contrast between the pmPFC and the pre-SMA was the representation of the spatial cue location in the former and its absence in the latter area. In individual neurons, neurons in pmPFC and pre-SMA had either single or mixed representation of tactics and action. Some of the pmPFC neurons additionally encoded cue location. Finally, neurons in the supplementary motor area mainly represented the action. Taken together, the present results indicate that, of these three areas, the pmPFC plays a cardinal role during the integration of behavioral tactics and visuospatial information when selecting an action.

Plasticity induction in the pre-supplementary motor area (pre-SMA) and SMA-proper differentially affects visuomotor sequence learning.

BACKGROUND: Both pre-supplementary motor area (pre-SMA) and SMA-proper (SMA) must play important roles in visuomotor sequence learning. However, functional differences between the pre-SMA and SMA have not been well studied in humans. OBJECTIVE: To elucidate the functional differences between the pre-SMA and SMA in sequence learning in humans. METHODS: To induce LTP/LTD, we administered quadripulse transcranial magnetic stimulation (QPS) with an inter-stimulus interval of 5 or 50 ms (QPS-5/50) over the pre-SMA or SMA in healthy volunteers. The sham stimulation was also done as a control. We studied the effects of LTP/LTD in the pre-SMA/SMA on a new sequence learning and the performance of well-learned sequence by using sequence learning task called the "2 × 10 task". Effects on the simple choice reaction time task were also studied for comparison. RESULTS: QPS-5 over the pre-SMA increased the error rate without any changes in movement speed. When administered over the SMA, QPS-5 decreased, and QPS-50 increased the rate of reaction time reduction across trials without changes in the error rate. QPS over neither the pre-SMA nor SMA affected the performances of a well-learned sequence or a simple choice reaction time task. CONCLUSIONS: Our findings that QPS over the pre-SMA correlated with sequence learning performance and that over the SMA with execution speed are consistent with the previous results in animals and humans. Our results lend further support to the utility of QPS for modulating motor learning in humans.

The modulatory role of pre-SMA in speed-accuracy tradeoff: A bi-directional TMS study.

Many perceptual decisions are inevitably subject to the tradeoff between speed and accuracy of choices (SAT). Sequential sampling models attribute this ubiquitous relation to random noise in the sensory evidence accumulation process, and assume that SAT is adaptively modulated by altering the decision thresholds at which the level of integrated evidence should reach for making a choice. Although, neuroimaging studies have shown a relationship between right presupplementary motor area (pre-SMA) activity and threshold setting, only a limited number of brain stimulation studies aimed at establishing the causal link, results of which were inconsistent. Additionally, these studies were limited in scope as they only examined the effect of pre-SMA activity unidirectionally through experimentally inhibiting the neural activity in this region. The current study aims to investigate the predictions of the striatal theory of SAT by experimentally assessing the modulatory effect of right pre-SMA on threshold setting bi-directionally. To this end, we applied both offline inhibition and excitation to the right pre-SMA utilizing transcranial magnetic stimulation in a within-subjects design and tested participants on a Random Dot Motion Task. Decision thresholds were estimated using the Hierarchical Drift Diffusion Model. Findings of our planned comparisons showed that right pre-SMA inhibition leads to significantly higher, whereas right pre-SMA excitation leads to significantly lower thresholds without showing any effects on the evidence integration process itself.

The presupplementary area within the language network: a resting state functional magnetic resonance imaging functional connectivity analysis.

The presupplementary motor area (pre-SMA) is involved in volitional selection. Despite the lateralization of the language network and different functions for both pre-SMA, few studies have reported the lateralization of pre-SMA activity and very little is known about the possible lateralization of pre-SMA connectivity. Via functional connectivity analysis, we sought to understand how the language network may be connected to other intrinsic connectivity networks (ICNs) through the pre-SMA. We performed a spatial independent component analysis of resting state functional magnetic resonance imaging in 30 volunteers to identify the language network. Subsequently, we applied seed-to-voxel functional connectivity analyses centered on peaks detected in the pre-SMA. Three signal peaks were detected in the pre-SMA. The left rostral pre-SMA intrinsic connectivity network (LR ICN) was left lateralized in contrast to bilateral ICNs associated to right pre-SMA peaks. The LR ICN was anticorrelated with the dorsal attention network and the right caudal pre-SMA ICN (RC ICN) anticorrelated with the default mode network. These two ICNs overlapped minimally. In contrast, the right rostral ICN overlapped the LR ICN. Both right ICNs overlapped in the ventral attention network (vATT). The bilateral connectivity of the right rostral pre-SMA may allow right hemispheric recruitment to process semantic ambiguities. Overlap between the right pre-SMA ICNs in vATT may contribute to internal thought to external environment reorientation. Distinct ICNs connected to areas involved in lexico-syntactic selection and phonology converge in the pre-SMA, which may constitute the resolution space of competing condition-action associations for speech production.