Patrick Jung

Human Motor Corpus Callosum: Topography, Somatotopy, and Link between Microstructure and Function

The corpus callosum (CC) is the principal white matter fiber bundle connecting neocortical areas of the two hemispheres. Although an object of extensive research, important details about the anatomical and functional organization of the human CC are still largely unknown. Here we focused on the callosal motor fibers (CMFs) that connect the primary motor cortices (M1) of the two hemispheres. Topography and somatotopy of CMFs were explored by using a combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure. CMF microstructure was assessed by fractional anisotropy (FA), and CMF functional connectivity between the hand areas of M1 was measured by interhemispheric inhibition using paired-pulse transcranial magnetic stimulation. CMFs mapped onto the posterior body and isthmus of the CC, with hand CMFs running significantly more anteriorly and ventrally than foot CMFs. FA of the hand CMFs but not FA of the foot CMFs correlated linearly with interhemispheric inhibition between the M1 hand areas. Findings demonstrate that CMFs connecting defined body representations of M1 map onto a circumscribed region in the CC in a somatotopically organized manner. The significant and topographically specific positive correlation between FA and interhemispheric inhibition strongly suggests that microstructure can be directly linked to functional connectivity. This provides a novel way of exploring human brain function that may allow prediction of functional connectivity from variability of microstructure in healthy individuals, and potentially, abnormality of functional connectivity in neurological or psychiatric patients.

Homeostatic and Nonhomeostatic Modulation of Learning in Human Motor Cortex

Motor learning is important throughout life for acquisition and adjustment of motor skill. The extent of motor learning may be modulated by the history of motor cortex activity, but little is known which metaplasticity rule (homeostatic vs nonhomeostatic) governs this interaction. Here, we explored in nine healthy adults the effects of three different paired associative stimulation (PAS) protocols on subsequent learning of rapid thumb flexion movements. PAS resulted in either a long-term potentiation (LTP)-like increase in excitability of the stimulated motor cortex (PASLTP), or a long-term depression (LTD)-like decrease (PASLTD), or no change (control condition, PASCON). Learning was indexed by the increase in peak acceleration of the trained movement. Delays of 0 and 90 min between PAS and motor practice were tested. At the 0 min delay, PASLTD strongly facilitated motor learning (homeostatic interaction), and PASLTP also facilitated learning, although to a lesser extent (nonhomeostatic interaction). At the 90 min delay, PASLTD facilitated learning, whereas PASLTP depressed learning (interactions both homeostatic). Therefore, facilitation of learning by previous brain stimulation occurs primarily and most effectively through homeostatic interactions, but at the 0 min delay, nonhomeostatic mechanisms such as LTP-induced blockade of LTD and nonsaturated LTP-induced facilitation of learning might also play a role. The present findings demonstrate that motor learning in humans can be modulated by noninvasive brain stimulation and suggest the possibility of enhancing motor relearning in defined neurological patients.

Asymmetry in the human primary somatosensory cortex and handedness.

Brain asymmetry is a phenomenon well known for handedness and language specialization and has also been studied in motor cortex. Less is known about hemispheric asymmetries in the somatosensory cortex. In the present study, we systematically investigated the representation of somatosensory function analyzing early subcortical and cortical somatosensory-evoked potentials (SEP) after electrical stimulation of the right and left median nerve. In 16 subjects, we compared thresholds, the peripheral neurogram at Erb point, and, using MRI-based EEG source analysis, the P14 brainstem component as well as N20 and P22, the earliest cortical responses from the primary sensorimotor cortex. Handedness was documented using the Edinburgh Inventory and a dichotic listening test was performed as a measure for language dominance. Whereas thresholds, Erb potential, and P14 were symmetrical, amplitudes of the cortical N20 showed significant hemispheric asymmetry. In the left hemisphere, the N20 amplitude was higher, its generator was located further medial, and it had a stronger dipole moment. There was no difference in dipole orientation. As a possible morphological correlate, the size of the left postcentral gyrus exceeded that of the right. The cortical P22 component showed a lower amplitude and a trend toward weaker dipole strength in the left hemisphere. Across subjects, there were no significant correlations between laterality indices of N20, the size of the postcentral gyrus, handedness, or ear advantage. These data show that asymmetry of median nerve SEP occurs at the cortical level, only. However, both functional and morphological cortical asymmetry of somatosensory representation appears to vary independently of motor and language functions.

Subtle hemispheric asymmetry of motor cortical inhibitory tone

OBJECTIVE To test whether a novel paired transcranial magnetic stimulation (TMS) protocol (J Physiol 545.1 (2002) 153) detects hemispheric differences in motor cortical inhibition. METHODS Nine right-handers and 8 left-handers participated. Focal paired TMS was applied to the hand area of the dominant (M1-D) or non-dominant motor cortex (M1-ND). Motor evoked potentials (MEP) were recorded from the relaxed contralateral abductor digiti minimi. The first (S1) and second pulse (S2) were separated by 1.5 or 2.1 ms. Nine stimulus intensities of S1 and S2 (i.e. 9x9 intensity conditions) ranging from 60 to 140% of resting motor threshold (RMT) were tested. The interaction between S1 and S2 was expressed by MEP(S1+S2)/(MEP(S1)+MEP(S2))*100%. Values below and above 100% indicate short-interval intracortical inhibition (SICI) and facilitation (SICF), respectively. RESULTS In right-handers, RMT was lower, SICI was present with fewer intensity conditions and the magnitude of SICI was less in M1-D than M1-ND. No hemispheric asymmetry was found for SICF. Left-handers showed no hemispheric difference for any of these measures. CONCLUSIONS Findings suggest that, in right-handers, M1-D is controlled by less inhibitory tone than M1-ND. This may put the M1-D to an advantage for processes that are associated with a reduction of SICI, such as voluntary activation and use-dependent plasticity.

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Hemispheric asymmetry of hand representation in human primary somatosensory cortex and handedness.

OBJECTIVE To evaluate interhemispheric differences of hand representation in primary somatosensory (SI) and motor (MI) cortices and its relation to handedness. METHODS MRI-based EEG dipole source analysis was performed separately for early (P14, N20, P22) and middle/late latency (P30, N60, N110) SEP components after left and right median nerve stimulation. In addition, the location of the MI hand area (Omega region) and handedness were determined. RESULTS Equivalent current dipoles (ECDs) of N20, P30 and N60 SEP components were localized in contralateral SI (area 3b, N20 and P30; area 1, N60), the mean P22 ECD localization was in area 4 of contralateral MI. In contrast to the Omega region and the precentral P22 component, ECDs in both areas 3b and 1 were located more laterally in the right than in the left hemisphere. ECDs in the right SI lay more laterally than the ipsilateral Omega region. Asymmetry in SI was not correlated with handedness. CONCLUSIONS The data demonstrate that the location of hand representation shows relevant hemispheric asymmetry in human SI, both in areas 3b and 1. SIGNIFICANCE Hemispheric asymmetry in SI must be considered in the studies on cortical reorganization and plasticity in SI as well as for transcranial magnetic stimulation (TMS) over SI.

Differences of the ipsilateral silent period in small hand muscles

The ipsilateral silent period (iSP) is thought to depend on activity transmitted by the corpus callosum but ipsilateral corticospinal pathways may also contribute. Because the presence of ipsilateral corticospinal pathways differs between small hand muscles, we compared the iSP in the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. The iSP was elicited in 20 healthy subjects by focal transcranial magnetic stimulation of one primary motor cortex during maximal voluntary contraction of the ipsilateral target muscle. The iSP duration was significantly longer in the FDI than APB because of an irregularly occurring second phase of inhibition in the FDI that was absent in the APB. Although the first phase of inhibition is transmitted by the corpus callosum, we provide evidence that the second phase is mediated through ipsilateral corticospinal pathways. Therefore, for specific assessment of callosal conduction, the iSP should be measured in the APB rather than FDI. Muscle Nerve, 2006

Motor callosal disconnection in early relapsing-remitting multiple sclerosis.

In relapsing‐remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0–2.0) to an age‐matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber‐tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA‐CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short‐interval interhemispheric inhibition (S‐IHI), an established measure of CMF effective connectivity. FA‐CC and S‐IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA‐CC) and function (S‐IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine‐hole‐peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S‐IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion. Hum Brain Mapp, 2011.

Chapter 3 Long-term potentiation (LTP)-like plasticity and learning in human motor cortex – investigations with transcranial magnetic stimulation (TMS)

Publisher Summary This chapter presents several experiments to demonstrate an interaction between motor learning and long-term potentiation (LTP)/long-term depression (LTD) in the human primary motor cortex (M1). The chapter explores the effects of motor learning on subsequent associative LTP/LTD-like plasticity and the effects of LTP/LTD-like plasticity on subsequent motor learning in specific ways, consistent with the Bienenstock–Cooper–Munro (BCM) theory of bidirectional synaptic plasticity. LTP-like plasticity is a mechanism of motor learning in humans, consistent with previous evidence from animal preparations. The results show that TMS offers the opportunity to study mechanisms of learning in human motor cortex. The findings support the view that learning depends on LTP and that principles of metaplasticity consistent with the BCM theory regulate learning. It appears that learning performance is enhanced when the probability for LTP induction is high because learning is an LTP-dependent process itself.

Structural and Functional Asymmetry in the Human Parietal Opercular Cortex

In this combined electroencephalographic and magnetic resonance imaging (MRI) study, the asymmetry of functional and structural measures in the human parietal operculum (PO) were investigated. Median nerve somatosensory evoked potential recordings showed maximum scalp potentials over contralateral (N80, N110) and ipsilateral (N100, N130) temporal electrode positions. In accordance, MRI-coregistered source analysis revealed two electrical sources in the contralateral (N80, N110) and two in the ipsilateral (N100, N130) PO. The dipole orientations of the contra- and ipsilateral sources with earlier peak activation, N80 and N100, were more tangential than those of the later peaking N110 and N130 sources. The most prominent contralateral N110 source exhibited pronounced left lateralized dipole strengths in the 80- to 120-ms latency range, in contrast to symmetrical N80 and ipsilateral source responses. The asymmetry of the N110 source activity explained both the asymmetry of N110 and N100 scalp potentials. Morphometric analysis demonstrated no interhemispheric differences in the sizes of the anterior PO (aPO), containing the cytoarchitectonic areas OP3 and OP4, but left lateralized sizes of the posterior PO (pPO), which encompasses the anatomically defined areas OP1 and OP2. The N110 source was located in the pPO and its asymmetry was significantly correlated with the structural pPO asymmetry but not with handedness and auditory lateralization. Thus both structural and functional asymmetries exist in the human PO and they are closely related to each other but not to measures of brain asymmetry in other functional systems, i.e., auditory lateralization and handedness.