Lateral Prefrontal Stimulation of Active Cortex With Theta Burst Transcranial Magnetic Stimulation Affects Subsequent Engagement of the Frontoparietal Network.

BACKGROUND: A critical unanswered question about therapeutic transcranial magnetic stimulation is what patients should do during treatment to optimize its effectiveness. Here, we address this lack of knowledge in healthy participants, testing the hypotheses that stimulating the left dorsolateral prefrontal cortex (dlPFC) while participants perform a working memory task will provide stronger effects on subsequent activation, perfusion, connectivity, and performance than stimulating resting dlPFC. METHODS: After a baseline functional magnetic resonance imaging session to localize dlPFC activation and the associated frontoparietal network (FPN) engaged by an n-back task, healthy participants (N = 40, 67.5% female) underwent 3 counterbalanced sessions, separated by several weeks, during which they received intermittent theta burst stimulation (iTBS) followed by magnetic resonance imaging scans as follows: 1) iTBS to the dlPFC while resting passively (passive), 2) iTBS to the dlPFC while performing the n-back task (active), and 3) iTBS to a vertex site, while not engaged in the n-back task and resting passively (control). RESULTS: We found no difference in n-back performance between the 3 conditions. However, FPN activation was reduced while performing the n-back task in the active condition relative to the passive and control conditions. There was no differential activity in the FPN on comparing passive with control conditions, i.e., there was no effect of the site of stimulation. We found no effects of state or site of stimulation on perfusion or connectivity with the dlPFC. CONCLUSIONS: In this study, the state of the brain while receiving iTBS affected FPN activation, possibly reflecting greater efficiency of FPN network activation when participants were stimulated while engaging the FPN.

The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest.

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes.

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode.

BACKGROUND: Few studies have investigated tolerability, blinding, and double-blinding of High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes above 2 milliamps (mA). OBJECTIVE: We examined a) tolerability of HD-tDCS during stimulation sessions and b) blinding and double blinding of participants and study team members. METHODS: Data from a mixed neurologic sample of 292 older adults were pooled from 3046 HD-tDCS sessions (2329 active; 717 sham). Per electrode amplitudes ranged from 1 mA to 4 mA with total currents up to 10 mA. Participants completed a standardized sensation (tolerability) questionnaire after each session. Participants and study team members stated whether the participant received active or sham stimulation at the end of various sessions. Data were collapsed into the presence/absence of a symptom due to low rates of positive responding and were analyzed for both differences and bioequivalency. RESULTS: There were no safety-related adverse events. HD-tDCS was well tolerated with mostly no ("none") or "mild" sensations reported across sessions, regardless of active or sham condition and in both stimulation naïve and experienced participants. There were no significant differences in side effects between active and sham, with some achieving bioequivalence. Tingling and itching were significantly more common after lower (<2 mA) than higher (≥3 mA) amplitude active sessions, while skin redness was significantly more common after higher amplitudes. Blinding was effective at the participant and study team levels. CONCLUSIONS: HD-tDCS was well tolerated with center electrode amplitudes up to 4 mA. The bimodal ramp-up/down format of the sham was effective for blinding. These results support higher scalp-based amplitudes that enable greater brain-based current intensities in older adults.

High Intensity Acute Aerobic Exercise Elicits Alterations in Circulating and Skeletal Muscle Tissue Expression of Neuroprotective Exerkines.

Background: Cathepsin B (CTSB) and brain derived neurotrophic factor (BDNF) are increased with aerobic exercise (AE) and skeletal muscle has been identified as a potential source of secretion. However, the intensity of AE and the potential for skeletal muscle contributions to circulating CTSB and BDNF have not been fully studied in humans. Objective: Determine the effects of AE intensity on circulating and skeletal muscle CTSB and BDNF expression profiles. Methods: Young healthy subjects (n = 16) completed treadmill-based AE consisting of VO2max and calorie-matched acute AE sessions at 40%, 65% and 80% VO2max. Fasting serum was obtained before and 30-minutes after each bout of exercise. Skeletal muscle biopsies (vastus lateralis) were taken before, 30-minutes and 3-hours after the 80% bout. Circulating CTSB and BDNF were assayed in serum. CTSB protein, BDNF protein and mRNA expression were measured in skeletal muscle tissue. Results: Serum CTSB increased by 20±7% (p = 0.02) and 30±18% (p = 0.04) after 80% and VO2max AE bouts, respectively. Serum BDNF showed a small non-significant increase (6±3%; p = 0.09) after VO2max. In skeletal muscle tissue, proCTSB increased 3 h-post AE (87±26%; p < 0.01) with no change in CTSB gene expression. Mature BDNF protein decreased (31±35%; p = 0.03) while mRNA expression increased (131±41%; p < 0.01) 3 h-post AE. Skeletal muscle fiber typing revealed that type IIa and IIx fibers display greater BDNF expression compared to type I (p = 0.02 and p < 0.01, respectively). Conclusions: High intensity AE elicits greater increases in circulating CTSB compared with lower intensities. Skeletal muscle protein and gene expression corroborate the potential role of skeletal muscle in generating and releasing neuroprotective exerkines into the circulation.NEW AND NOTEWORTHY: 1) CTSB is enriched in the circulation in an aerobic exercise intensity dependent manner. 2) Skeletal muscle tissue expresses both message and protein of CTSB and BDNF. 3) BDNF is highly expressed in glycolytic skeletal muscle fibers.

Measuring Hand Sensory Function and Force Control in Older Adults: Are Current Hand Assessment Tools Enough?

BACKGROUND: The ability to grasp and manipulate objects is essential for performing activities of daily living. However, there is limited information regarding age-related behavioral differences in hand sensorimotor function due, in part, to the lack of assessment tools capable of measuring subtle but important differences in hand function. The purpose of this study was to demonstrate performance differences in submaximal force control and tactile pattern recognition in healthy older adults using 2 custom-designed sensorimotor assessment tools. METHODS: Sensorimotor function was assessed in 13 healthy older adults (mean age 72.2 ± 5.5 years, range: 65-84 years) and 13 young adults (mean age 20 ± 1.4 years, range: 19-23 years). Clinical assessments included the Montreal Cognitive Assessment (MoCA), monofilament testing, maximum voluntary contraction (MVC), and Grooved Pegboard Test. Sensorimotor assessments included submaximal (5, 20% MVC) grip force step-tracking and tactile pattern recognition tasks. RESULTS: Clinical assessments revealed no or minimal group differences in MVC, monofilament thresholds, and MoCA. However, sensorimotor assessments showed that older adults took longer to discriminate tactile patterns and had poorer accuracy than young adults. Older adults also produced submaximal forces less smoothly than young adults at the 20% force level while greater variability in force maintenance was seen at 5% but not 20% MVC. CONCLUSIONS: These results demonstrate the ability to integrate higher-order tactile information and control low grip forces is impaired in older adults despite no differences in grip strength or cognition. These findings underscore the need for more sensitive evaluation methods that focus on sensorimotor ability reflective of daily activities.

Interhemispheric interactions between the right angular gyrus and the left motor cortex: a transcranial magnetic stimulation study.

The interconnection of the angular gyrus of right posterior parietal cortex (PPC) and the left motor cortex (LM1) is essential for goal-directed hand movements. Previous work with transcranial magnetic stimulation (TMS) showed that right PPC stimulation increases LM1 excitability, but right PPC followed by left PPC-LM1 stimulation (LPPC-LM1) inhibits LM1 corticospinal output compared with LPPC-LM1 alone. It is not clear if right PPC-mediated inhibition of LPPC-LM1 is due to inhibition of left PPC or to combined effects of right and left PPC stimulation on LM1 excitability. We used paired-pulse TMS to study the extent to which combined right and left PPC stimulation, targeting the angular gyri, influences LM1 excitability. We tested 16 healthy subjects in five paired-pulsed TMS experiments using MRI-guided neuronavigation to target the angular gyri within PPC. We tested the effects of different right angular gyrus (RAG) and LM1 stimulation intensities on the influence of RAG on LM1 and on influence of left angular gyrus (LAG) on LM1 (LAG-LM1). We then tested the effects of RAG and LAG stimulation on LM1 short-interval intracortical facilitation (SICF), short-interval intracortical inhibition (SICI), and long-interval intracortical inhibition (LICI). The results revealed that RAG facilitated LM1, inhibited SICF, and inhibited LAG-LM1. Combined RAG-LAG stimulation did not affect SICI but increased LICI. These experiments suggest that RAG-mediated inhibition of LAG-LM1 is related to inhibition of early indirect (I)-wave activity and enhancement of GABAB receptor-mediated inhibition in LM1. The influence of RAG on LM1 likely involves ipsilateral connections from LAG to LM1 and heterotopic connections from RAG to LM1.NEW & NOTEWORTHY Goal-directed hand movements rely on the right and left angular gyri (RAG and LAG) and motor cortex (M1), yet how these brain areas functionally interact is unclear. Here, we show that RAG stimulation facilitated right hand motor output from the left M1 but inhibited indirect (I)-waves in M1. Combined RAG and LAG stimulation increased GABAB, but not GABAA, receptor-mediated inhibition in left M1. These findings highlight unique brain interactions between the RAG and left M1.

Reduced Facilitation of Parietal-Motor Functional Connections in Older Adults.

Age-related changes in cortico-cortical connectivity in the human motor network in older adults are associated with declines in hand dexterity. Posterior parietal cortex (PPC) is strongly interconnected with motor areas and plays a critical role in many aspects of motor planning. Functional connectivity measures derived from dual-site transcranial magnetic stimulation (dsTMS) studies have found facilitatory inputs from PPC to ipsilateral primary motor cortex (M1) in younger adults. In this study, we investigated whether facilitatory inputs from PPC to M1 are altered by age. We used dsTMS in a conditioning-test paradigm to characterize patterns of functional connectivity between the left PPC and ipsilateral M1 and a standard pegboard test to assess skilled hand motor function in 13 young and 13 older adults. We found a PPC-M1 facilitation in young adults but not older adults. Older adults also showed a decline in motor performance compared to young adults. We conclude that the reduced PPC-M1 facilitation in older adults may be an early marker of age-related decline in the neural control of movement.

Reversal of Visual Feedback Modulates Somatosensory Plasticity.

Reversed visual feedback during unimanual training increases transfer of skills to the opposite untrained hand and modulates plasticity in motor areas of the brain. However, it is unclear if unimanual training with reversed visual feedback also affects somatosensory areas. Here we manipulated visual input during unimanual training using left-right optical reversing spectacles and tested whether unimanual training with reversed vision modulates somatosensory cortical excitability to facilitate motor performance. Thirty participants practiced a unimanual ball-rotation task using the right hand with either left-right reversed vision (incongruent visual and somatosensory feedback) or direct vision (congruent feedback) of the moving hand. We estimated cortical excitability in primary somatosensory cortex (S1) before and after unimanual training by measuring somatosensory evoked potentials (SEPs). This was done by electrically stimulating the median nerve in the wrist while participants rested, and recording potentials over both hemispheres using electroencephalography. Performance of the ball-rotation task improved for both the right (trained) and left (untrained) hand after training across both direct and reversed vision conditions. Participants with direct vision of the right hand during training showed SEPs amplitudes increased bilaterally. In contrast, participants in the reversed visual condition showed attenuated SEPs following training. The results suggest that cortical suppression of S1 activity supports skilled motor performance after unimanual training with reversed vision, presumably by sensory gating of afferent signals from the movement. This finding provides insight into the mechanisms by which visual input interacts with the sensorimotor system and induces neuroplastic changes in S1 to support skilled motor performance.

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation.

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has provided important insights into fundamental processes of the brain like cognition, learning, and motor control. However, this approach cannot provide causal evidence for the involvement of brain areas of interest. Transcranial magnetic stimulation (TMS) is a powerful, noninvasive tool for studying the human brain that can overcome this limitation by transiently modifying brain activity. Here, we highlight recent advances using a paired-pulse, dual-site TMS method with two coils that causally probes cortico-cortical interactions in the human motor system during different task contexts. Additionally, we describe a dual-site TMS protocol based on cortical paired associative stimulation (cPAS) that transiently enhances synaptic efficiency in two interconnected brain areas by applying repeated pairs of cortical stimuli with two coils. These methods can provide a better understanding of the mechanisms underlying cognitive-motor function as well as a new perspective on manipulating specific neural pathways in a targeted fashion to modulate brain circuits and improve behavior. This approach may prove to be an effective tool to develop more sophisticated models of brain-behavior relations and improve diagnosis and treatment of many neurological and psychiatric disorders.

Using Dual-Site Transcranial Magnetic Stimulation to Probe Connectivity between the Dorsolateral Prefrontal Cortex and Ipsilateral Primary Motor Cortex in Humans.

Dual-site transcranial magnetic stimulation to the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) can be used to probe functional connectivity between these regions. The purpose of this study was to characterize the effect of DLPFC stimulation on ipsilateral M1 excitability while participants were at rest and contracting the left- and right-hand first dorsal interosseous muscle. Twelve participants were tested in two separate sessions at varying inter-stimulus intervals (ISI: 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, and 20 ms) at two different conditioning stimulus intensities (80% and 120% of resting motor threshold). No significant effect on ipsilateral M1 excitability was found when applying a conditioning stimulus over DLPFC at any specific inter-stimulus interval or intensity in either the left or right hemisphere. Our findings suggest neither causal inhibitory nor faciliatory influences of DLPFC on ipsilateral M1 activity while participants were at rest or when performing an isometric contraction in the target hand muscle.

Somatosensory-motor cortex interactions measured using dual-site transcranial magnetic stimulation.

BACKGROUND: Dual-site transcranial magnetic stimulation (ds-TMS) is a neurophysiological technique to measure functional connectivity between cortical areas. OBJECTIVE/HYPOTHESIS: To date, no study has used ds-TMS to investigate short intra-hemispheric interactions between the somatosensory areas and primary motor cortex (M1). METHODS: We examined somatosensory-M1 interactions in the left hemisphere in six experiments using ds-TMS. In Experiment 1 (n = 16), the effects of different conditioning stimulus (CS) intensities on somatosensory-M1 interactions were measured with 1 and 2.5 ms inter-stimulus intervals (ISIs). In Experiment 2 (n = 16), the time-course of somatosensoy-M1 interactions was studied using supra-threshold CS intensity at 6 different ISIs. In Experiment 3 (n = 16), the time-course of short-interval cortical inhibition (SICI) and effects of different CS intensities on SICI were measured similar to Experiments 1 and 2. Experiment 4 (n = 13) examined the effects of active contraction on SICI and somatosensory-M1 inhibition. Experiments 5 and 6 (n = 10) examined the interactions between SAI with either 1 ms SICI or somatosensory-M1 inhibition. RESULTS: Experiments 1 and 2 revealed reduced MEP amplitudes when applying somatosensory CS 1 ms prior to M1 TS with 140 and 160% CS intensities. Experiment 3 demonstrated that SICI at 1 and 2.5 ms did not correlate with somatosensory-M1 inhibition. Experiment 4 found that SICI but not somatosensory-M1 inhibition was abolished with active contraction. The results of Experiments 5-6 showed SAI was disinhibited in presence of somatosensory-M1 while SAI was increased in presence of SICI. CONCLUSION: Collectively, the results support the notion that the somatosensory areas inhibit the ipsilateral M1 at very short latencies.

Learning from Goal and Action Based Observations Differentially Modulates Functional Motor Cortical Plasticity.

Action observation can facilitate motor skill learning and lead to a memory trace in motor representations of action. However, it remains unclear whether the action itself or the goal of the action drive changes in motor representations after learning by observation. We performed two experiments. In Experiment 1, using serial reaction time task and transcranial magnetic stimulation, we showed that observation of right-hand actions during skill learning only increased left motor cortical excitability, leading to behavioral gains in the same hand as the observed hand. In contrast, observing a sequence of visual cue positions devoid of hand action increases motor cortical excitability in both hemispheres and facilitates motor skill learning in the right hand (Experiment 1) and left hand for a mirror-symmetric sequence (Experiment 2). We propose that the encoding of observed movements maps onto motor representations of the same action to form a limb-specific motor memory, whereas the learning of spatial goals forms memory traces in the motor representations in both hemispheres to prepare for potential action in either hand.

Rubber hand illusion modulates the influences of somatosensory and parietal inputs to the motor cortex.

The rubber hand illusion (RHI) paradigm experimentally produces an illusion of rubber hand ownership and arm shift by simultaneously stroking a rubber hand in view and a participant's visually occluded hand. It involves visual, tactile, and proprioceptive multisensory integration and activates multisensory areas in the brain, including the posterior parietal cortex (PPC). Multisensory inputs are transformed into outputs for motor control in association areas such as PPC. A behavioral study reported decreased motor performance after RHI. However, it remains unclear whether RHI modifies the interactions between sensory and motor systems and between PPC and the primary motor cortex (M1). We used transcranial magnetic stimulation (TMS) and examined the functional connections from the primary somatosensory and association cortices to M1 and from PPC to M1 during RHI. In experiment 1, short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) were measured before and immediately after a synchronous (RHI) or an asynchronous (control) condition. In experiment 2, PPC-M1 interaction was measured using two coils. We found that SAI and LAI were reduced in the synchronous condition compared with baseline, suggesting that RHI decreased somatosensory processing in the primary sensory and the association cortices projecting to M1. We also found that greater inhibitory PPC-M1 interaction was associated with stronger RHI assessed by questionnaire. Our findings suggest that RHI modulates both the early and late stages of processing of tactile afferent, which leads to altered M1 excitability by reducing the gain of somatosensory afferents to resolve conflicts among multisensory inputs. NEW & NOTEWORTHY Perception of one's own body parts involves integrating different sensory information and is important for motor control. We found decreased effects of cutaneous stimulation on motor cortical excitability during rubber hand illusion (RHI), which may reflect decreased gain of tactile input to resolve multisensory conflicts. RHI strength correlated with the degree of inhibitory posterior parietal cortex-motor cortex interaction, indicating that parietal-motor connection is involved in resolving sensory conflicts and body ownership during RHI.

Functional interaction between human dorsal premotor cortex and the ipsilateral primary motor cortex for grasp plans: a dual-site TMS study.

Recent findings suggest that the dorsal premotor cortex (PMd), a cortical area in the dorsomedial pathway, is involved in grasp control. It is unclear, however, whether human PMd transfers grasp-related information to the primary motor cortex hand area (M1HAND) during action preparation. The present study tested whether ipsilateral cortico-cortical connections between PMd and M1HAND in the left hemisphere are modulated during grasp preparation. Ten participants performed object-directed grasps and reaches with the right hand. Functional connectivity between left PMd and ipsilateral M1HAND was probed with dual-site transcranial magnetic stimulation. We found that PMd-M1HAND functional interactions were facilitated selectively for the muscles involved in the preparation of the upcoming grasps. The PMd-M1HAND interaction was facilitated for first dorsal interosseous muscle for both precision grip and whole-hand grasps and for abductor digiti minimi muscle for whole-hand grasps. We conclude that human dorsomedial PMd-M1HAND circuit encodes handgrip formation during grasp preparation.

Changes in corticospinal excitability associated with motor learning by observing.

While many of our motor skills are acquired through physical practice, we can also learn how to make movements by observing others. For example, individuals can learn how to reach in novel dynamical environments ('force fields', FF) by observing the movements of a tutor. Previous neurophysiological and neuroimaging studies in humans suggest a role for the motor system in motor learning by observing. Here, we tested the role of primary motor cortex (M1) in motor learning by observing. We used single-pulse transcranial magnetic stimulation to elicit motor-evoked potentials (MEPs) in hand muscles at rest. MEPs were elicited before and after participants observed either a video showing a tutor adapting her reaches to an FF or a control video showing a tutor performing reaches in an unlearnable FF. During MEP acquisition, participants fixated a crosshair while their hand muscles were relaxed. We predicted that observing motor learning would result in greater increases in offline M1 excitability compared to observing movements that did not involve learning. We found that observing FF learning resulted in subsequent increases in MEP amplitudes recorded from right first dorsal interosseous and right abductor pollicis brevis muscles at rest. There were no changes in MEP amplitudes after control participants observed a tutor performing similar movements but not learning. The observed MEP changes can thus be specifically linked to observing motor learning. These results are consistent with the idea that observing motor learning produces functional changes in M1, corticospinal networks or both.

Increases in motor cortical excitability during mirror visual feedback of a precision grasp is influenced by vision and movement of the opposite limb.

Unimanual grasp movements with mirrored visual feedback (MVF) can improve function and increase excitability of primary motor cortex (M1) ipsilateral to the moving hand. However, no study to date has examined the contribution of vision and movement of the opposite hand during an object-directed precision grasp. In this study, we tested 15 healthy individuals in three conditions: MVF (vision + motor), Movement (motor component), and Action Observation (vision component). We hypothesized that unimanual grasp movements with MVF increases the excitability and reduces intracortical inhibition of the M1 ipsilateral to the moving hand. We found increased excitability in the right primary motor cortex (M1) ipsilateral to the moving right hand for MVF movements compared to Rest (Baseline). In contrast, no change was found in right M1 with only movement of the right hand or observation of object-directed precision grasp with left hand. We also found a reduction in short-interval intracortical inhibition in MVF movements compared to baseline. These findings suggest that excitability in M1 during an object-directed precision grasp is mediated by the combination of viewing the movement performed and performing the movement from the opposite hand.

Modulation of cognitive cerebello-cerebral functional connectivity by lateral cerebellar continuous theta burst stimulation.

Network connectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has revealed the contribution of distinct cerebellar lobules to an array of brain wide networks sub-serving motor and cognitive processes. As distinct cerebellar lobules form relatively accessible nodes of different brain networks, this raises the possibility for site-specific modulation of network connectivity using non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). Continuous theta burst transcranial magnetic stimulation (cTBS) induces long-lasting inhibition of cortical areas. Although previous studies have shown that cTBS of the lateral cerebellum modulates motor cortical excitability and improves symptoms in several movement disorders, the effect on cognitive domains has not been examined. We explored the immediate effects of cTBS in a sham-controlled study on the strength of intrinsic functional connectivity between cerebellar and cortical motor and cognitive regions in 12 participants. Lateral cerebellar cTBS significantly decreased functional connectivity with frontal and parietal cognitive regions, while connectivity with motor regions remained unaltered. Sham stimulation had no effect on either motor or cognitive connectivity. These results show that inhibitory cerebellar stimulation reduces intrinsic functional connectivity between different cortical areas, in keeping with the known connectivity pattern of the cerebellum. The results highlight the plasticity of cerebello-cerebral networks and indicate for the first time that this functional connectivity can be downregulated using an inhibitory neurostimulation paradigm. This may shed light on the pathophysiology of network dysfunction and is a potential treatment for cognitive and movement disorders.

Human dorsomedial parieto-motor circuit specifies grasp during the planning of goal-directed hand actions.

According to one influential view, two specialized parieto-frontal circuits control prehension: a dorsomedial stream for hand transport during reaching and a dorsolateral stream for preshaping the fingers during grasping. However, recent evidence argues that an area within the dorsomedial stream-macaque area V6A and, its putative human homolog, superior parietal occipital cortex (SPOC) - encodes both hand transport and grip formation. We tested whether planning varied hand actions modulates functional connectivity between left SPOC and ipsilateral primary motor cortex (M1) using a dual-site, paired-pulse transcranial magnetic stimulation paradigm with two coils (dsTMS). Participants performed three different hand actions to a target object comprising a small cylinder atop a larger cylinder. These actions were: reaching-to-grasp the top (GT) using a precision grip, reaching-to-grasp the bottom (GB) using a whole-hand grip, or reaching-to-touch (Touch) the side of the target object without forming a grip. Motor-evoked potentials (MEPs) from TMS to M1, with or without preceding TMS to SPOC, were recorded from first dorsal interosseous (FDI) and abductor digiti minimi (ADM) hand muscles in two experiments that varied timing parameters (the stimulus onset asynchrony, SOA, between the 'GO' cue and stimulation and interpulse interval, IPI, between SPOC and M1 stimulation). We found that preparatory response amplitudes in the SPOC-M1 circuit of different hand muscles were selectively modulated early in the motor plan for different types of grasps. First, based on SPOC-M1 interactions, across two experiments, the role of the ADM was facilitated during a whole-hand grasp of a large object (GB) relative to other conditions under certain timing parameters (SOA = 150 msec; IPI = 6 msec). Second, the role of the FDI was facilitated during hand action planning compared to rest. These findings suggest that the human dorsomedial parieto-motor stream plays a causal role in planning grip formation for object-directed actions.

Parietal area BA7 integrates motor programs for reaching, grasping, and bimanual coordination.

Skillful interaction with the world requires that the brain uses a multitude of sensorimotor programs and subroutines, such as for reaching, grasping, and the coordination of the two body halves. However, it is unclear how these programs operate together. Networks for reaching, grasping, and bimanual coordination might converge in common brain areas. For example, Brodmann area 7 (BA7) is known to activate in disparate tasks involving the three types of movements separately. Here, we asked whether BA7 plays a key role in integrating coordinated reach-to-grasp movements for both arms together. To test this, we applied transcranial magnetic stimulation (TMS) to disrupt BA7 activity in the left and right hemispheres, while human participants performed a bimanual size-perturbation grasping task using the index and middle fingers of both hands to grasp a rectangular object whose orientation (and thus grasp-relevant width dimension) might or might not change. We found that TMS of the right BA7 during object perturbation disrupted the bimanual grasp and transport/coordination components, and TMS over the left BA7 disrupted unimanual grasps. These results show that right BA7 is causally involved in the integration of reach-to-grasp movements of the two arms. NEW & NOTEWORTHY: Our manuscript describes a role of human Brodmann area 7 (BA7) in the integration of multiple visuomotor programs for reaching, grasping, and bimanual coordination. Our results are the first to suggest that right BA7 is critically involved in the coordination of reach-to-grasp movements of the two arms. The results complement previous reports of right-hemisphere lateralization for bimanual grasps.