The cerebellum's contribution to beat interval discrimination.

From expert percussionists to individuals who cannot dance, there are widespread differences in people's abilities to perceive and synchronize with a musical beat. The aim of our study was to identify candidate brain regions that might be associated with these abilities. For this purpose, we used Voxel-Based-Morphometry to correlate inter-individual differences in performance on the Harvard Beat Assessment Tests (H-BAT) with local inter-individual variations in gray matter volumes across the entire brain space in 60 individuals. Analysis revealed significant co-variations between performances on two perceptual tasks of the Harvard Beat Assessment Tests associated with beat interval change discrimination (faster, slower) and gray matter volume variations in the cerebellum. Participant discrimination thresholds for the Beat Finding Interval Test (quarter note beat) were positively associated with gray matter volume variation in cerebellum lobule IX in the left hemisphere and crus I bilaterally. Discrimination thresholds for the Beat Interval Test (simple series of tones) revealed the tendency for a positive association with gray matter volume variations in crus I/II of the left cerebellum. Our results demonstrate the importance of the cerebellum in beat interval discrimination skills, as measured by two perceptual tasks of the Harvard Beat Assessment Tests. Current findings, in combination with evidence from patients with cerebellar degeneration and expert dancers, suggest that cerebellar gray matter and overall cerebellar integrity are important for temporal discrimination abilities.

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.

Predicting Motor Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0-3) or poor (modified NIHSS 4-8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8-17), and the median modified NIHSS score was 5 (interquartile range = 2-8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78-1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.

Sleep-dependent motor memory plasticity in the human brain.

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.

Examining rhythm and melody processing in young children using FMRI.

While it is often reported that musical experience can have positive effects on cognitive development in young children, the neural basis of such potential effects remains relatively unexplored. Employing functional magnetic resonance imaging (fMRI) for such research presents as many challenges as possibilities, not least of which is the fact that young children can find it difficult to remain still and attentive for long periods of time. Here we describe an fMRI scanning protocol designed specifically for young children using short scanning runs, a sparse temporal sampling data acquisition technique, simple rhythmic and melodic discrimination tasks with a button-press response, and a child-oriented preparation session. Children were recruited as part of a large-scale longitudinal study examining the effects of musical training on cognitive development and the structure and function of the growing brain. Results from an initial analysis of 33 children and from the first five children to be re-scanned after musical training indicate that our scanning protocol is successful and that activation differences can be detected both between conditions and over time.

Structural asymmetries in the human forebrain and the forebrain of non-human primates and rats.

Possible asymmetries of the following structures were studied: volumes of total human hemispheres, cortex and white matter volumes in post-mortem- (unknown handedness) and living brains (male right-handers); volumes of the rat primary visual cortex, its mon- and binocular subfields, its layer iv and the density of myelinated fibres in layer iv; transmitter receptor densities (NMDA, AMPA, kainate and GABAA receptors) in sensorimotor regions of the rat cortex; volume of the motor cortex and the 3D-extent of the central sulcus in the post-mortem- (unknown handedness) and living human brain (male right-handers); petalia of the hemispheres in human (male right- and left-handers) and chimpanzee brains. Histological, MRI and receptor autoradiographic techniques were used. With the notable exceptions of the transmitter receptors and the total primary visual cortex in rats and the hemispheres in chimpanzees, which do not show any significant directional asymmetry, all other parameters studied are asymmetrically distributed between the right- and left hemispheres. The regional distribution pattern and the degree of asymmetry of frontal and occipital petalia in living human brains differ between right- and left-handers.

Individual integration of positron emission tomography and high-resolution magnetic resonance imaging.

We have developed, validated, and employed a technique of retrospective spatial alignment and integrated display of positron emission tomographic (PET) and high-resolution magnetic resonance (MR) brain images. The method was designed to improve the anatomical evaluation of functional images obtained from single subjects. In the first computational step, alignment of PET and MR data sets is achieved by iteratively matching in three orthogonal views the outermost scalp contours derived from front-to-back projections of each data set. This procedure avoids true three-dimensional modeling, runs without user interaction, and tolerates missing parts of the head circumference in the image volume, as usually the case with PET. Thereafter, high-resolution MR sections corresponding to the PET slices are reconstructed from the spatially transformed MR data. In a phantom study of this method, PET/MR alignment of the phantom's surface was accurate with average residual misfits of 2.17 to 2.32 mm as determined in three orthogonal planes. In-plane alignment of the phantom's insertion holes was accurate with an average residual misfit of 2.30 mm. In vivo application in six subjects allowed the individual anatomical localization of regional CBF (rCBF) responses obtained during unilateral manual exploration. In each subject, the maxima of the rCBF activations in the hand area were precisely allocated to gray matter in the anterior or posterior wall of the central sulcus. The configuration of the rCBF responses closely followed the gyral structures. The technique provided a better topographical understanding of rCBF changes in subtraction images of PET activation studies. It opens the perspective for studies of structural-functional relationships in individual subjects.

Quantitation of regional cerebral blood flow with 15O-butanol and positron emission tomography in humans.

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.

Quantitative analysis of the columnar arrangement of neurons in the human cingulate cortex.

The spatial organization of human cingulate (areas 24b, 23b, and 31) and pericingulate (areas 7 and 19) cortex was examined by using an image analyzer to measure characteristics of vertically oriented, translaminar columns of neurons in the cerebral cortex. Columns of 30-50 microns in diameter are hypothesized to be a general feature of cortical organization, but no quantitative analysis of different human cortical areas has been performed. Our results prove for the first time that a columnar organization was detectable in every area examined. The average width of cell columns was approximately 40 microns separated by a neuropil-rich fascicle of the same dimension. Because differences in the expression of a columnar organization were seen, the degree of columnization was subsequently expressed by a verticality index (VI) revealing specific changes in its dimension depending on the architectonic area. The VI was calculated by a linear combination of three variables derived from the measurement of cell density profiles in Nissl-stained sections at right angles to vertically oriented cell columns. Variables included the amplitude of profile peaks, the standard deviation of the width of those profile peaks, and the standard deviation of the distances between profile peaks. The index of verticality describes the deviation of a distinct area and layer from the mean degree of vertical organization of all cortical areas and layers examined. Thus, different degrees of columnar organization can be quantitatively described by the verticality index and can be used as criteria to characterize architectonic areas.

Quantitative cytoarchitectonics of the posterior cingulate cortex in primates.

The cytoarchitecture of four cortical areas within the posterior cingulate region and the differences among them are quantitatively analyzed in 17 primate species. The transition from allocortex (area 29) to isocortex (areas 30, 23, and 31) is characterized by shifts in laminar proportions and cellular densities. The molecular layer and inner main lamina (layers V and VI) occupy a smaller proportion of the cortex in iso- than in allocortex, while conversely, the outer main lamina (layers II and III) makes up a larger proportion of the cortex in iso- than in allocortex. Layer IV is relatively larger in area 31 than in area 23. The packing densities of cell bodies were determined by gray-level index values. These values show that the isocortex has lower cell densities in the outer main lamina, but higher cell densities in the inner main layers. Furthermore, the granular layer of area 31 is more densely packed than it is in area 23. These results are discussed as structural correlates of a relative increase in the receptive and processing capacities of the isocortex over the adjacent allocortex.

Comparative aspects of the primate posterior cingulate cortex.

Cytoarchitecturally defined cortical areas of the posterior cingulate gyrus differ morphometrically among the major taxonomic divisions of primates. Prosimians and anthropoids have different laminar proportions in the isocortical regions (areas 30, 23, and 31); anthropoids have relatively larger outer main laminae and granular layers than prosimians. In the granular retrosplenial cortex (area 29), however, prosimians and anthropoids differ only in the proportion of the molecular layer to the rest of the cortex. On the other hand, the proportions of the inner and outer main laminae of area 29 differ between the infraorder divisions of Anthropoidea, the catarrhines, and the platyrrhines. The platyrrhines (New World monkeys) have apparently specialized by increasing the outer main lamina of area 29, which contains afferent and intracortical connections. Among all primates, the amount of neuropil in each cortical region changes as a function of brain weight, but within each area, the neuropil maintains a constant ratio between the outer and inner laminae. These observations suggest that neuropil ratios are conservative features in primates and that evolutionary changes more frequently involve shifts in volumetric proportions. Furthermore, the platyrrhine-catarrhine differences in area 29 likely evolved after the prosimian-anthropoid differences were established in the isocortical cingulate regions.

Diffusion-weighted imaging and National Institutes of Health Stroke Scale in the acute phase of posterior-circulation stroke.

BACKGROUND: Occlusive disease of the posterior circulation represents a heterogeneous group of strokes that differ in etiology, clinical presentation, and prognosis. Computed tomography provides suboptimal visualization of posterior-circulation infarcts. Anatomic definition of traditional magnetic resonance imaging sequences has been used for clinicoradiologic correlation in patients with posterior-circulation disease. These studies focused on the subacute rather than the acute phase of ischemia. Lesion volumes on diffusion-weighted imaging (DWI) and perfusion imaging were found to have a good correlation with 24-hour National Institutes of Health stroke scale (NIHSS) score in ischemia of the anterior circulation. Correlation between NIHSS score and lesion volume in posterior-circulation infarcts is unknown. OBJECTIVES: To investigate whether DWI is useful for clinicoradiologic correlation of posterior-circulation ischemia within 24 hours after symptom onset and whether NIHSS score correlates with lesion volumes in patients with posterior-circulation stroke. PATIENTS AND METHODS: In a database analysis of 631 patients with stroke from June 26, 1996, to July 30, 1999, 115 patients (18%) had symptoms of posterior-circulation ischemia by imaging and clinical criteria. Among these 115, we included all patients (n = 40) who underwent DWI within 24 hours from symptom onset (mean, 9.7 +/- 7.1 hours). All 40 patients also underwent magnetic resonance angiography and T2-weighted imaging. Seventy-five did not meet inclusion criteria: in 45, magnetic resonance imaging was performed more than 24 hours after symptom onset; 12 did not have DWI; in 11 patients, symptoms resolved within 24 hours; 6 had hemorrhages; and 1 had a border zone infarct. RESULTS: An acute lesion on DWI corresponding to the patient's symptoms was detected in all 40 patients, 16 (40%) of whom had detectable acute lesions on T2-weighted images. The lesions on DWI were larger in 11 of the 16 patients with positive T2-weighted images. Acute lesion volume did not correlate with NIHSS score (n = 40; rho = 0.30; P =.06, Spearman rank) also when DWI lesion volumes were divided by cause and territory. CONCLUSIONS: Diffusion-weighted imaging is more effective than T2-weighted imaging in patients with acute posterior-circulation strokes. The DWI lesion volume did not significantly correlate with NIHSS score, suggesting that NIHSS is more weighted toward anterior-circulation stroke symptoms.

Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke.

Diffusion-weighted MRI can rapidly detect acute cerebral ischemic injury as hyperintense signal changes, reflecting a decline in the apparent diffusion coefficient (ADC) of water through brain parenchyma, whereas ADC is elevated in the chronic stage because of increased extracellular water content. To determine the time course of these ADC changes, we analyzed 157 diffusion-weighted MRI studies performed at varying time points from the initial ischemic event from 101 patients. Data were expressed as the relative ADC (rADC), the ratio of lesion to control regions of interest. We observed two phases in the time course of rADC changes in acute human stroke: a significant (p < 0.005) reduction in rADC lasting for at least 96 hours from stroke onset (mean, 58.3% of control; SEM, 1.47) and an increasing trend from reduction to pseudonormalization to elevation of rADC values at later subacute to chronic time points (> or = 7 days). We suggest that the persistent reduction of rADC within the first four days may reflect ongoing or progressive cytotoxic edema to a greater degree than extracellular edema and cell lysis.

Comparison of EPISTAR and T2*-weighted gadolinium-enhanced perfusion imaging in patients with acute cerebral ischemia.

PURPOSE: To compare echo-planar imaging with signal targeting and alternating radiofrequency (EPISTAR), an arterial spin-labeling technique, to a T2*-weighted gadolinium-enhanced (T2*-WGE) MR perfusion technique for the evaluation of acute cerebrovascular disease. METHOD: Twenty-one EPISTAR and T2*-WGE perfusion studies were performed on 18 patients with the clinical diagnosis of acute stroke (12 men, 6 women, age range 34 to 89 years, mean age 68 years). For qualitative analysis, perfusion studies of both techniques were grouped into categories (hyperperfusion, normal perfusion, delayed perfusion, or absent perfusion) and compared with a Wilcoxon signed rank test. Quantitative analysis was performed using signal intensity measurements in a region of interest that was defined by diffusion-weighted imaging abnormalities. These signal intensity measurements were compared with a mirror region in the contralateral unaffected hemisphere. Signal intensity ratios (infarcted region versus the unaffected contralateral region) were calculated and compared using a paired t test. RESULTS: Qualitative analysis demonstrated agreement between the two techniques in 17 of 21 studies (hyperfusion, n = 3 patients; normal perfusion, n = 3; delayed perfusion, n = 4; and absent perfusion, n = 7). In four studies, the two techniques disagreed when EPISTAR demonstrated absent and T2*-WGE perfusion demonstrated delayed perfusion (p > 0.05). Quantitative analysis revealed a mean signal intensity ratio of 0.73 +/- 0.79 for the T2*-WGE perfusion technique and 0.69 +/- 0.68 for the EPISTAR technique (p > 0.05). CONCLUSION: The noninvasive EPISTAR technique can assess perfusion abnormalities similarly to the T2*-WGE perfusion technique and may provide a valuable alternative in the diagnosis of acute stroke patients. Differences between the two techniques can be explained by the applied inflow times in the EPISTAR technique.

Sex but no hand difference in the isthmus of the corpus callosum.

We performed high-resolution magnetic resonance morphometry of the total midsagittal area and seven midsagittal subareas of the corpus callosum in healthy young adult dextrals and sinistrals (N = 52). There was no influence of handedness on these anatomic measurements. However, an effect of sex emerged, with women (N = 26) having a larger proportional isthmus segment of the callosum. This may reflect a sex-specific difference in the interhemispheric connectivity and functional organization of the temporoparietal association cortex.

Multiple acute stroke syndrome: marker of embolic disease?

OBJECTIVE: To determine the frequency and etiologic significance of multiple acute ischemic lesions in stroke. BACKGROUND: Although patients may have more than one stroke during the course of their lives, acute ischemic stroke is usually thought of as a single event. Using diffusion-weighted imaging (DWI), an MRI technique that detects ischemic injury within minutes after onset, we have often observed multiple acute ischemic lesions. METHODS: The MRI scans of 59 consecutively studied patients were reviewed to determine the frequency and etiologic significance of multiple acute ischemic lesions on DWI. RESULTS: Multiple acute ischemic lesions were present in 10 (17%) of 59 patients. The lesions usually occurred within one major circulation (anterior or posterior), but in two patients (3%), lesions occurred in both cerebral hemispheres or in the anterior and the posterior circulations. The lesions often were small and resulted from presumed multiple emboli or the break-up of an embolus. Two patients had internal carotid artery occlusive disease and four had a cardiac or aortic source. In the other four patients the source was not determined. Lesions larger than 1 cm in diameter progressed to infarction, but some smaller lesions were not seen on follow-up T2-weighted imaging. CONCLUSIONS: Multiple acute stroke lesions on DWI are common and could be caused by multiple emboli or the breakup of an embolus. In some cases it might become possible to make early inferences concerning the stroke mechanism that could be of use for immediately directing the clinical work-up and treatment of the patient.

Topography of interictal glucose hypometabolism in unilateral mesiotemporal epilepsy.

We mapped the regional cerebral glucose metabolism (rCMRGlu) in 20 patients suffering from medically refractory focal epilepsy of either left or right mesiotemporal origin (mTLE) during resting wakefulness. After temporal lobectomy, histology demonstrated hippocampal sclerosis in 18 patients. Pixel-by-pixel comparisons with healthy control subjects showed significant (p < 0.001) depressions of the mean rCMRGlu ipsilateral to the epileptic focus in the mesiotemporal region, including the hippocampus and the parahippocampal gyrus and middle temporal gyrus. Additional remote rCMRGlu depressions occurred bilaterally in the fronto-orbital cortex and ipsilaterally in the posterior insula and the thalamus. Patients with left-sided mTLE had additional rCMRGlu depressions in the left inferior frontal gyrus (Broca's region) and superior temporal gyrus at the parietotemporal junction, whereas corresponding rCMRGlu depressions were not present in patients with right mTLE. Neuropsychological testing showed impaired verbal fluency, verbal intelligence, and verbal memory in the left mTLE patients. Correlations of the specific mean rCMRGlu depressions and the neuropsychological deficits suggest that impaired language functions in patients with left mTLE could result from functional changes beyond the temporal lobe.

Ictal motor signs and interictal regional cerebral hypometabolism.

Early motor manifestations are the main components of focal seizures involving the frontal lobe. We examined the relationship between the initial ictal motor manifestations and interictal abnormalities of cerebral glucose consumption (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of neocortical origin. Group data analysis revealed that patients with predominantly unilateral clonic seizures had a significant contralateral perirolandic hypometabolism and to a lesser degree a contralateral frontomesial hypometabolism. Patients with predominantly focal tonic manifestations showed a hypometabolism within the frontomesial and perirolandic regions that was unilateral in all patients with lateralized tonic seizures. Patients with versive seizures had mainly contralateral metabolic depressions without a consistent regional pattern. Patients with hypermotor seizures had metabolic depressions involving frontomesial, anterior cingulate, perirolandic, and anterior insular/frontal operculum areas. In all patient groups, bilateral and symmetric hypometabolism of the thalamus and cerebellum was observed. We propose that this pattern of distinctly abnormal metabolic brain regions demonstrates not only possible epileptogenic zones but also symptomatogenic brain regions as shown by the associations between clinical manifestations and sets of abnormal brain regions, particularly if epileptogenic zones are in a clinically silent neocortical brain region. The detection and possible differentiation of symptomatogenic and epileptogenic zones might improve the effectiveness of presurgical noninvasive studies.

EEG-triggered echo-planar functional MRI in epilepsy.

We investigated whether: (1) EEG recordings could be successfully performed in an MRI imager, (2) subclinical epileptic discharges could be used to trigger ultrafast functional MRI images, (3) artifact-free functional MRI images could be obtained while the patient was having the EEG monitored, and (4) the functional MRI images so obtained would show focal signal increases in relation to epileptic discharges. We report our results in two patients who showed focally higher signal intensity, reflective of increased local blood flow, in ultrafast functional MRI timed to epileptic discharges recorded while the patients were in the imager and compared with images not associated with discharges. One patient showed a focal increase despite a clinical and EEG history of generalized discharges. This approach may have the potential to identify brain regions activated during brief focal epileptic discharges.

The ischemic penumbra: operationally defined by diffusion and perfusion MRI.

BACKGROUND: Identifying tissue at risk for infarction is important in deciding which patients would benefit most from potentially harmful therapies and provides a way to evaluate newer therapies with regard to the amount of ischemic tissue salvaged. OBJECTIVE: To operationally define and characterize cerebral tissue at risk for stroke progression. METHODS: We retrospectively selected 25 patients with an acute onset of a hemispheric stroke from our database who had undergone a combination of two diffusion-weighted MRI studies and a perfusion-weighted MRI study. We applied a logistic regression model using maps of the relative mean transit time and relative cerebral blood flow (rCBF) as well as three different maps of the relative cerebral blood volume (rCBV) to predict an operationally defined penumbra (region of mismatch between the diffusion lesion on day 1 and its extension 24 to 72 hours later). RESULTS: Maps of the rCBF and initial rCBV were significant predictors for identifying penumbral tissue. Our operationally defined penumbral region was characterized by a reduction in the initial rCBV (47% of contralateral control region [CCR]), an increase (163% of CCR) in the total rCBV, and a reduction (37% of CCR) in the rCBF, whereas the operationally defined ischemic core showed a more severe reduction in the rCBF (12% of CCR) and in the initial rCBV (19% of CCR). CONCLUSION: These MR indexes may allow the identification and quantification of viable but ischemically threatened cerebral tissue amenable to therapeutic interventions in the hyperacute care of stroke patients.