Age and visual cortex inhibition: a TMS-MRS study.

Paired-pulse transcranial magnetic stimulation is a valuable tool for investigating inhibitory mechanisms in motor cortex. We recently demonstrated its use in measuring cortical inhibition in visual cortex, using an approach in which participants trace the size of phosphenes elicited by stimulation to occipital cortex. Here, we investigate age-related differences in primary visual cortical inhibition and the relationship between primary visual cortical inhibition and local GABA+ in the same region, estimated using magnetic resonance spectroscopy. GABA+ was estimated in 28 young (18 to 28 years) and 47 older adults (65 to 84 years); a subset (19 young, 18 older) also completed a paired-pulse transcranial magnetic stimulation session, which assessed visual cortical inhibition. The paired-pulse transcranial magnetic stimulation measure of inhibition was significantly lower in older adults. Uncorrected GABA+ in primary visual cortex was also significantly lower in older adults, while measures of GABA+ that were corrected for the tissue composition of the magnetic resonance spectroscopy voxel were unchanged with age. Furthermore, paired-pulse transcranial magnetic stimulation-measured inhibition and magnetic resonance spectroscopy-measured tissue-corrected GABA+ were significantly positively correlated. These findings are consistent with an age-related decline in cortical inhibition in visual cortex and suggest paired-pulse transcranial magnetic stimulation effects in visual cortex are driven by GABAergic mechanisms, as has been demonstrated in motor cortex.

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.

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.

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.

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.

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.

Paired-Pulse Parietal-Motor Stimulation Differentially Modulates Corticospinal Excitability across Hemispheres When Combined with Prism Adaptation.

Rightward prism adaptation ameliorates neglect symptoms while leftward prism adaptation (LPA) induces neglect-like biases in healthy individuals. Similarly, inhibitory repetitive transcranial magnetic stimulation (rTMS) on the right posterior parietal cortex (PPC) induces neglect-like behavior, whereas on the left PPC it ameliorates neglect symptoms and normalizes hyperexcitability of left hemisphere parietal-motor (PPC-M1) connectivity. Based on this analogy we hypothesized that LPA increases PPC-M1 excitability in the left hemisphere and decreases it in the right one. In an attempt to shed some light on the mechanisms underlying LPA's effects on cognition, we investigated this hypothesis in healthy individuals measuring PPC-M1 excitability with dual-site paired-pulse TMS (ppTMS). We found a left hemisphere increase and a right hemisphere decrease in the amplitude of motor evoked potentials elicited by paired as well as single pulses on M1. While this could indicate that LPA biases interhemispheric connectivity, it contradicts previous evidence that M1-only MEPs are unchanged after LPA. A control experiment showed that input-output curves were not affected by LPA per se. We conclude that LPA combined with ppTMS on PPC-M1 differentially alters the excitability of the left and right M1.

The time course for visual extinction after a 'virtual' lesion of right posterior parietal cortex.

Our understanding of the attentional networks in the human brain largely relies on neuropsychological studies in patients with lesions to the posterior parietal cortex (PPC), particularly in the right hemisphere, that may cause severe disruptions of attentional functions. However, lesion studies only capture a point in time when the dysfunctions caused by the damage have triggered a chain of adaptive responses in the brain. To disentangle deficits and ensuing cortical plasticity, here we examined the time course for one's ability to detect objects in the visual periphery after an inhibitory continuous theta-burst stimulation (cTBS) protocol to the left or right PPC. Our results showed that cTBS of right PPC caused participants to be less sensitive to objects appearing on the left side as well as to objects appearing on both sides at the same time, consistent with an overall shift of attention to the right side of space. In addition, we found that participants missed more objects during bilateral presentations similar to patients with visual extinction. Critically, extinction evolved over time; that is, visual extinction for ipsilateral objects improved after 10 min whereas contralateral extinction peaked around 15-25 min after cTBS. Our findings suggest that lesions to the PPC impair competition between the two visual hemifields, resulting in contralateral extinction as a secondary response, arguably due to ensuing disruptions in interhemispheric balance.

The right anterior intraparietal sulcus is critical for bimanual grasping: a TMS study.

Grasping with 2 limbs in opposition to one another is older than the hand, yet the neural mechanisms for bimanual grasps remain unclear. Similar to unimanual grasping, bimanual grasping may require regions in the parietal cortex that use visual object-feature information to find matching stable grasp points on the object. The localization of matching points is computationally expensive, so it might make sense for the signals to converge in a single cortical area. To examine this, we use transcranial magnetic stimulation (TMS) to probe the contribution of cortical areas known to be associated with unimanual grasping, while participants performed bimanual grasps. We applied TMS to the anterior and caudal portion of the intra-parietal sulcus (aIPS and cIPS) in each hemisphere during a size-perturbation task using the index fingers of both hands to grasp an object whose orientation might or might not change. We found significant interaction effects between TMS and perturbation of the grasp-relevant object dimension that increased grip aperture only for the right aIPS. These results indicate that the aIPS is involved not only in unimanual, but also bimanual grasping, and the right aIPS is critically involved in bimanual grasps. This suggests that information from both hemispheres converges in the right hemisphere to achieve bimanual grasps.

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.

Repeated spaced cortical paired associative stimulation promotes additive plasticity in the human parietal-motor circuit.

OBJECTIVE: Repeated spaced sessions of repetitive transcranial magnetic stimulation (TMS) to the human primary motor cortex can lead to dose-dependent increases in motor cortical excitability. However, this has yet to be demonstrated in a defined cortical circuit. We aimed to examine the effects of repeated spaced cortical paired associative stimulation (cPAS) on excitability in the motor cortex. METHODS: cPAS was delivered to the primary motor cortex (M1) and posterior parietal cortex (PPC) with two coils. In the multi-dose condition, three sessions of cPAS were delivered 50-min apart. The single-dose condition had one session of cPAS, followed by two sessions of a control cPAS protocol. Motor-evoked potentials were evaluated before and up to 40 min after each cPAS session as a measure of cortical excitability. RESULTS: Compared to a single dose of cPAS, motor cortical excitability significantly increased after multi-dose cPAS. Increasing the number of cPAS sessions resulted in a cumulative, dose-dependent effect on excitability in the motor cortex, with each successive cPAS session leading to notable increases in potentiation. CONCLUSION: Repeated spaced cPAS sessions summate to increase motor cortical excitability induced by single cPAS. SIGNIFICANCE: Repeated spaced cPAS could potentially restore abilities lost due to disorders like stroke.

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.

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.

Specialization of reach function in human posterior parietal cortex.

Posterior parietal cortex (PPC) plays an important role in the planning and control of goal-directed action. Single-unit studies in monkeys have identified reach-specific areas in the PPC, but the degree of effector and computational specificity for reach in the corresponding human regions is still under debate. Here, we review converging evidence spanning functional neuroimaging, parietal patient and transcranial magnetic stimulation studies in humans that suggests a functional topography for reach within human PPC. We contrast reach to saccade and grasp regions to distinguish functional specificity and also to understand how these different goal-directed actions might be coordinated at the cortical level. First, we present the current evidence for reach specificity in distinct modules in PPC, namely superior parietal occipital cortex, midposterior intraparietal cortex and angular gyrus, compared to saccade and grasp. Second, we review the evidence for hemispheric lateralization (both for hand and visual hemifield) in these reach representations. Third, we review evidence for computational reach specificity in these regions and finally propose a functional framework for these human PPC reach modules that includes (1) a distinction between the encoding of reach goals in posterior-medial PPC as opposed to reach movement vectors in more anterior-lateral PPC regions, and (2) their integration within a broader cortical framework for reach, grasp and eye-hand coordination. These findings represent both a confirmation and extension of findings that were previously reported for the monkey.

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.

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.

Specificity of human parietal saccade and reach regions during transcranial magnetic stimulation.

Single-unit recordings in macaque monkeys have identified effector-specific regions in posterior parietal cortex (PPC), but functional neuroimaging in the human has yielded controversial results. Here we used on-line repetitive transcranial magnetic stimulation (rTMS) to determine saccade and reach specificity in human PPC. A short train of three TMS pulses (separated by an interval of 100 ms) was delivered to superior parieto-occipital cortex (SPOC), a region over the midposterior intraparietal sulcus (mIPS), and a site close to caudal IPS situated over the angular gyrus (AG) during a brief memory interval while subjects planned either a saccade or reach with the left or right hand. Behavioral measures then were compared to controls without rTMS. Stimulation of mIPS and AG produced similar patterns: increased end-point variability for reaches and decreased saccade accuracy for contralateral targets. In contrast, stimulation of SPOC deviated reach end points toward visual fixation and had no effect on saccades. Contralateral-limb specificity was highest for AG and lowest for SPOC. Visual feedback of the hand negated rTMS-induced disruptions of the reach plan for mIPS and AG, but not SPOC. These results suggest that human SPOC is specialized for encoding retinally peripheral reach goals, whereas more anterior-lateral regions (mIPS and AG) along the IPS possess overlapping maps for saccade and reach planning and are more closely involved in motor details (i.e., planning the reach vector for a specific hand). This work provides the first causal evidence for functional specificity of these parietal regions in healthy humans.

TMS over human frontal eye fields disrupts trans-saccadic memory of multiple objects.

We recently showed that transcranial magnetic stimulation (TMS) over the right parietal eye fields disrupts memory of object features and locations across saccades. We applied TMS over the frontal eye fields (FEF) as subjects compared the feature details of visual targets presented either within a single eye fixation (Fixation Task) or across a saccade (Saccade Task). TMS pulses were randomly delivered at one of 3 time intervals around the time of the saccade, or at equivalent times in the Fixation Task. A No-TMS control confirmed that subjects could normally retain approximately 3 visual features. TMS in the Fixation Task had no effect compared with No-TMS, but differences among TMS times were found during right FEF stimulation. TMS over either the right or left FEF disrupted memory performance in the Saccade Task when stimulation coincided most closely with the saccade. The capacity to compare pre-and postsaccadic features was reduced to 1-2 objects, as expected if the spatial aspect of memory was disrupted. These findings suggest that the FEF plays a role in the spatial processing involved in trans-saccadic memory of visual features. We propose that this process employs saccade-related feedback signals similar to those observed in spatial updating.

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.