Helmuth Steinmetz

In vivo evidence of structural brain asymmetry in musicians.

Certain human talents, such as musical ability, have been associated with left-right differences in brain structure and function. In vivo magnetic resonance morphometry of the brain in musicians was used to measure the anatomical asymmetry of the planum temporale, a brain area containing auditory association cortex and previously shown to be a marker of structural and functional asymmetry. Musicians with perfect pitch revealed stronger leftward planum temporale asymmetry than nonmusicians or musicians without perfect pitch. The results indicate that outstanding musical ability is associated with increased leftward asymmetry of cortex subserving music-related functions.

Increased corpus callosum size in musicians.

Using in-vivo magnetic resonance morphometry it was investigated whether the midsagittal area of the corpus callosum (CC) would differ between 30 professional musicians and 30 age-, sex- and handedness-matched controls. Our analyses revealed that the anterior half of the CC was significantly larger in musicians. This difference was due to the larger anterior CC in the subgroup of musicians who had begun musical training before the age of 7. Since anatomic studies have provided evidence for a positive correlation between midsagittal callosal size and the number of fibers crossing through the CC, these data indicate a difference in interhemispheric communication and possibly in hemispheric (a)symmetry of sensorimotor areas. Our results are also compatible with plastic changes of components of the CC during a maturation period within the first decade of human life, similar to those observed in animal studies.

Carotid Intima-Media Thickening Indicates a Higher Vascular Risk Across a Wide Age Range Prospective Data From the Carotid Atherosclerosis Progression Study (CAPS)

Background and Purpose— Carotid intima-media thickness (IMT) is an independent predictor of vascular events in age groups >45 years. However, there is little information about the predictive value of IMT in younger individuals. Methods— In the Carotid Atherosclerosis Progression Study (CAPS; n=5056; age range 19 to 90 years; mean age 50.1 years), common carotid artery (CCA) IMT, bifurcation IMT, internal carotid artery IMT and vascular risk factors were evaluated at baseline. The incidence of stroke, myocardial infarction (MI), and death was determined prospectively. Data for younger (<50 years; n=2436) and older subjects (≥50 years; n=2620) were analyzed separately using Cox proportional hazard regression models. Results— During a mean follow-up period of 4.2 years, there were 228 cases of MI, 107 strokes, and 50 deaths. IMT at all carotid segments was highly predictive of all end points (eg, hazard rate ratios [HRRs] per 1 SD CCA-IMT increase were 1.43 [95% CI: 1.35 to 1.51] for MI, 1.47 [1.35 to 1.60] for stroke, and 1.45 [1.38 to 1.52] for MI, stroke or death; all P<0.0001). Even after adjustment for age, sex, and vascular risk factors, the predictive value of CCA-IMT and bifurcation IMT remained significant for MI and the combined end point. For the latter, the HRRs were considerably higher in the younger than in the older age group (eg, HRR per 0.1 mm CCA-IMT was 1.34 [1.16 to 1.55] vis-à-vis 1.10 [1.05 to 1.15]; P=0.011 for age-IMT interaction). Conclusions— Carotid IMT independently predicts future vascular events. Its predictive value is at least as high in younger subjects as in older subjects.

Asymmetry in the human motor cortex and handedness.

Handedness is one of the most obvious functional asymmetries, but its relation to an anatomical asymmetry of the hand representation area in the motor cortex has not been demonstrated. This would be a crucial test for the hypothesis of structure-function correlation in cortical motor organization. Using magnetic resonance morphometry, we show for the first time that the depth of the central sulcus is related to handedness. In right-handers, the left central sulcus is deeper than the right, and vice versa in left-handers. Macrostructural asymmetry is complemented by a microstructural left-larger-than-right asymmetry in neuropil volume (i.e., tissue compartment containing dendrites, axons, and synapses) in Brodmanns area 4. These asymmetries suggest that hand preference is associated with increased connectivity (demonstrated by an increased neuropil compartment in left area 4) and an increased intrasulcal surface of the precentral gyrus in the dominant hemisphere.

Motor cortex and hand motor skills: Structural compliance in the human brain

Recent studies in humans and nonhuman primates have shown that the functional organization of the human sensorimotor cortex changes following sensory stimulation or following the acquisition of motor skills. It is unknown whether functional plasticity in response to the acquisition of new motor skills and the continued performance of complicated bimanual movements for years is associated with structural changes in the organization of the motor cortex. Professional musicians, especially keyboard and string players, are a prototypical group for investigating these changes in the human brain. Using magnetic resonance images, we measured the length of the posterior wall of the precentral gyrus bordering the central sulcus (intrasulcal length of the precentral gyrus, ILPG) in horizontal sections through both hemispheres of right‐handed keyboard players and of an age‐ and handedness‐matched control group. Lacking a direct in vivo measurement of the primary motor cortex in humans, we assumed that the ILPG is a measure of the size of the primary motor cortex. Left‐right asymmetry in the ILPG was analyzed and compared between both groups. Whereas controls exhibited a pronounced left‐larger‐than‐right asymmetry, keyboard players had more symmetrical ILPG. The most pronounced differences in ILPG between keyboard players and controls were seen in the most dorsal part of the presumed cortical hand representation of both hemispheres. This was especially true in the nondominant right hemispheres. The size of the ILPG was negatively correlated with age of commencement of musical training in keyboard players, supporting our hypothesis that the human motor cortex can exhibit functionally induced and long‐lasting structural adaptations. Hum. Brain Mapping 5:206–215, 1997.

Plaque Ulceration and Lumen Thrombus Are the Main Sources of Cerebral Microemboli in High-grade Internal Carotid Artery Stenosis

BACKGROUND AND PURPOSE Previous work has shown that rates of cerebral microemboli downstream of high-grade internal carotid artery stenosis are higher in recently symptomatic compared with asymptomatic patients. In addition, microembolic rates decline after carotid endarterectomy. We conducted a prospective investigation of 40 consecutive asymptomatic or recently symptomatic patients undergoing carotid endarterectomy for 70% to 95% internal carotid artery stenosis to determine the relationship between microembolic rate and pathoanatomic features of the carotid plaque. METHODS Transcranial Doppler monitoring including automated emboli detection was performed preoperatively to assess the rate of cerebral microemboli of the ipsilateral middle cerebral artery. The corresponding endarterectomy specimens were evaluated histologically with respect to the occurrence of plaque fissuring, intraplaque hemorrhage, plaque ulceration, or intraluminal thrombosis. RESULTS There were strong associations between plaque ulceration, intraluminal thrombosis, and downstream cerebral microemboli (P < or = .005, respectively). There were no correlations of microembolism with plaque fissuring or intraplaque hemorrhage (P = .82 and P = .28, respectively). CONCLUSIONS We conclude that ulceration and luminal thrombosis of the atheromatous plaque are the main sources of downstream cerebral microemboli in patients with high-grade internal carotid artery stenosis. Our data support the view that these pathoanatomic features may also play a key role in symptom development.

NADPH Oxidase Plays a Central Role in Blood-Brain Barrier Damage in Experimental Stroke

Background and Purpose— Cerebral ischemia/reperfusion is associated with reactive oxygen species (ROS) generation, and NADPH oxidases are important sources of ROS. We hypothesized that NADPH oxidases mediate blood-brain barrier (BBB) disruption and contribute to tissue damage in ischemia/reperfusion. Methods— Ischemia was induced by filament occlusion of the middle cerebral artery in mice for 2 hours followed by reperfusion. BBB permeability was measured by Evans blue extravasation. Monolayer permeability was determined from transendothelial electrical resistance of cultured porcine brain capillary endothelial cells. Results— BBB permeability was increased in the ischemic hemisphere 1 hour after reperfusion. In NADPH oxidase–knockout (gp91phox−/−) mice, middle cerebral artery occlusion–induced BBB disruption and lesion volume were largely attenuated compared with those in wild-type mice. Inhibition of NADPH oxidase by apocynin prevented BBB damage. In porcine brain capillary endothelial cells, hypoxia/reoxygenation induced translocation of the NADPH oxidase activator Rac-1 to the membrane. In vivo inhibition of Rac-1 by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin or Clostridium difficile lethal toxin B also prevented the ischemia/reperfusion–induced BBB disruption. Stimulation of porcine brain capillary endothelial cells with H2O2 increased permeability, an effect attenuated by inhibition of phosphatidyl inositol 3-kinase or c-Jun N-terminal kinase but not blockade of extracellular signal–regulated kinase-1/2 or p38 mitogen-activated protein kinase. Inhibition of Rho kinase completely prevented the ROS-induced increase in permeability and the ROS-induced polymerization of the actin cytoskeleton. Conclusions— Activation of Rac and subsequently of the gp91phox containing NADPH oxidase promotes cerebral ROS formation, which then leads to Rho kinase–mediated endothelial cell contraction and disruption of the BBB. Inhibition of NAPDH oxidase is a promising approach to reduce brain injury after stroke.

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.

Interhemispheric asymmetry of the human motor cortex related to handedness and gender.

Most people are right-handed, preferring the right hand for skilled as well as unskilled activities, but a notable proportion are mixed-handed, preferring to use the right hand for some actions and the left hand for others. Assuming a structural/functional correlation in the motor system we tested whether asymmetries in hand performance in consistent right and left handers as well as in mixed handers are associated with anatomical asymmetries in the motor cortex. In vivo MR morphometry was used for analyzing interhemispheric asymmetry in the depth of the central sulcus in the region of cortical hand representation of 103 healthy subjects. Subjects were tested both for hand preference and hand performance. As expected, left-right differences in hand performance differed significantly between consistent right, consistent left and mixed handers and were independent on gender. Male consistent right handers showed a significant deeper central sulcus on the left hemisphere than on the right. Anatomical asymmetries decreased significantly from male consistent right over mixed to consistent left handers. Sixty two per cent of consistent left handers revealed a deeper central sulcus on the right than on the left hemisphere, but for the group as a whole this rightward asymmetry was not significant. No interhemispheric asymmetry was found in females. Thus, anatomical asymmetry was associated with handedness only in males, but not in females, suggesting sex differences in the cortical organization of hand movements.

The Neural Circuitry Involved in the Reading of German Words and Pseudowords: A PET Study

Silent reading and reading aloud of German words and pseudowords were used in a PET study using (15O) butanol to examine the neural correlates of reading and of the phonological conversion of legal letter strings, with or without meaning. The results of 11 healthy, right-handed volunteers in the age range of 25 to 30 years showed activation of the lingual gyri during silent reading in comparison with viewing a fixation cross. Comparisons between the reading of words and pseudo-words suggest the involvement of the middle temporal gyri in retrieving both the phonological and semantic code for words. The reading of pseudowords activates the left inferior frontal gyrus, including the ventral part of Brocas area, to a larger extent than the reading of words. This suggests that this area might be involved in the sublexical conversion of orthographic input strings into phonological output codes. (Pre)motor areas were found to be activated during both silent reading and reading aloud. On the basis of the obtained activation patterns, it is hypothesized that the articulation of high-frequency syllables requires the retrieval of their concomitant articulatory gestures from the SMA and that the articulation of low-frequency syllables recruits the left medial premotor cortex.