Built on an analogy between the visual and auditory systems, the following dual stream model for language processing was suggested recently: a dorsal stream is involved in mapping sound to articulation, and a ventral stream in mapping sound to meaning. The goal of the study presented here was to test the neuroanatomical basis of this model. Combining functional magnetic resonance imaging (fMRI) with a novel diffusion tensor imaging (DTI)-based tractography method we were able to identify the most probable anatomical pathways connecting brain regions activated during two prototypical language tasks. Sublexical repetition of speech is subserved by a dorsal pathway, connecting the superior temporal lobe and premotor cortices in the frontal lobe via the arcuate and superior longitudinal fascicle. In contrast, higher-level language comprehension is mediated by a ventral pathway connecting the middle temporal lobe and the ventrolateral prefrontal cortex via the extreme capsule. Thus, according to our findings, the function of the dorsal route, traditionally considered to be the major language pathway, is mainly restricted to sensory-motor mapping of sound to articulation, whereas linguistic processing of sound to meaning requires temporofrontal interaction transmitted via the ventral route.DTI ͉ extreme capsule ͉ fMRI ͉ language networks ͉ arcuate fascicle ͉ extreme capsule

Only recently have neuroimaging studies moved away from describing regions activated by noxious stimuli and started to disentangle subprocesses within the nociceptive system. One approach to characterizing the role of individual regions is to record brain responses evoked by different stimulus intensities. We used such a parametric single-trial functional MRI design in combination with a thulium:yttrium-aluminium-granate infrared laser and investigated pain, stimulus intensity and stimulus awareness (i.e. pain-unrelated) responses in nine healthy volunteers. Four stimulus intensities, ranging from warm to painful (300-600 mJ), were applied in a randomized order and rated by the subjects on a five-point scale (P0-4). Regions in the dorsolateral prefrontal cortex and the intraparietal sulcus differentiated between P0 (not perceived) and P1 but exhibited no further signal increase with P2, and were related to stimulus perception and subsequent cognitive processing. Signal changes in the primary somatosensory cortex discriminated between non-painful trials (P0 and P1), linking this region to basic sensory processing. Pain-related regions in the secondary somatosensory cortex and insular cortex showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with signal changes for painful trials (P2-4). This was also true for the amygdala, with the exception that, in P0 trials in which the stimulus was not perceived (i.e. 'uncertain' trials), the evoked signal changes were as great as in P3 trials, indicating that the amygdala is involved in coding 'uncertainty', as has been suggested previously in relation to classical conditioning.

No abstract

Language acquisition in humans relies on abilities like abstraction and use of syntactic rules, which are absent in other animals. The neural correlate of acquiring new linguistic competence was investigated with two functional magnetic resonance imaging (fMRI) studies. German native speakers learned a sample of 'real' grammatical rules of different languages (Italian or Japanese), which, although parametrically different, follow the universal principles of grammar (UG). Activity during this task was compared with that during a task that involved learning 'unreal' rules of language. 'Unreal' rules were obtained manipulating the original two languages; they used the same lexicon as Italian or Japanese, but were linguistically illegal, as they violated the principles of UG. Increase of activation over time in Broca's area was specific for 'real' language acquisition only, independent of the kind of language. Thus, in Broca's area, biological constraints and language experience interact to enable linguistic competence for a new language.

Neuroimaging studies have demonstrated activations in the anterior cingulate cortex (ACC) related to the affective component of pain, but not to stimulus intensity. However, it is possible that the low spatial resolution of positron emission tomography, as used in the majority of these studies, obscured areas coding stimulus intensity. We revisited this issue, using a parametric single-trial functional magnetic resonance imaging design, and investigated pain, stimulus intensity, and stimulus awareness (i.e., pain unrelated) responses within the ACC in nine healthy volunteers. Four different stimulus intensities ranging from warm to painful (300-600 mJ) were applied with a thulium yttrium-aluminum granate infrared laser in a randomized order and rated by the subjects on a five point scale (P0-P4).Pain-related regions in the ventral posterior ACC showed a response that did not distinguish between innocuous trials (P0 and P1) but showed a positive linear relationship with the blood oxygenation level-dependent contrast signal for painful trials (P2-P4). Regions in the dorsal anterior ACC along the cingulate sulcus differentiated between P0 (not perceived) and P1 but exhibited no additional signal increase with P2; these regions are related to stimulus awareness and probably to cognitive processing. Most importantly, we identified a region in the dorsal posterior ACC showing a response that discriminated between nonpainful trials (P0 and P1); therefor, this region was simply related to basic sensory processing and not to pain intensity. Stimulus-related activations were all located adjacent to the cingulate motor area, highlighting the strategic link of stimulus processing and response generation in the posterior ACC.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative system disorder affecting both upper and lower motor neurons. Despite supportive electrophysiological investigations, the involvement of the upper motor neuron is often difficult to assess at an early stage of disease. Diffusion tensor MRI provides an estimate of the orientation of fibre bundles in white matter on the basis of the diffusion characteristics of water. Diffusivity is generally higher in directions along fibre tracts than perpendicular to them. This degree of directionality of diffusion can be measured as fractional anisotropy. Changes in tissue structure due to degeneration of the corticospinal fibres can lead to a modification of the degree of directionality which can be detected by diffusion tensor MRI. We investigated 15 patients with ALS, six of whom had no clinical signs of upper motor neuron involvement at the time of MRI investigation, but developed pyramidal tract symptoms later in the course of their disease. These patients met the El Escorial criteria as their disease progressed. We found a decrease in fractional anisotropy in the corticospinal tract, corpus callosum and thalamus in all 15 ALS patients, including the patients without clinical signs of upper motor neuron lesion, compared with healthy controls. Regression analysis showed a negative correlation between fractional anisotropy and central motor conduction time obtained by transcranial magnetic stimulation, allowing spatial differentiation between the degenerated corticospinal tract fibres that supply the upper and lower extremities. Thus, diffusion tensor MRI can be used to assess upper motor neuron involvement in ALS patients before clinical symptoms of corticospinal tract lesion become apparent, and it may therefore contribute to earlier diagnosis of motor neuron disease.

No abstract

According to the basal ganglia-thalamocortical circuit model, dopamine depletion in the nigrostriatal system leads to hypoactivation in the supplementary motor area (SMA) and the primary motor cortex (M1) in Parkinson's disease. This functional cortical deafferentation and its reversibility by levodopa (L-dopa) treatment has been established in previous studies for SMA but remains controversial for M1. We used functional MRI (fMRI) and a simple finger opposition task to correlate blood oxygenation level-dependent (BOLD) signal changes with motor performance, assessed separately for each hand between fMRI scanning sessions. Eight drug-naive patients with an akinetic idiopathic hemiparkinsonian syndrome (Hoehn and Yahr stage 1-1.5) and 10 healthy controls were studied. Patients performed a simple, auditory-paced random finger- opposition task every 3 s before and repeatedly every 20 min after intake of 300 mg of fast-release L-dopa. M1 contralateral to the affected hand and SMA, predominantly of the contralateral side, showed a BOLD signal increase after L-dopa intake. Furthermore, comparing BOLD responses of M1 and SMA between the patients and controls revealed that these areas were hypoactive before L-dopa treatment. Signal changes in M1 and SMA were highly correlated with motor performance, which increased after L-dopa intake. This result is not confounded by a performance effect because the motor task employed during scanning was identical throughout all sessions. In contrast to previous imaging studies in which cortical reorganization in Parkinson's disease was thought to have caused M1 hyperactivation, our data are in accordance with the hypothesis that, in de novo idiopathic hemiparkinsonian syndrome, motor cortex hypoactivation in contralateral M1 and bilateral SMA is caused by a decreased input from the subcortical motor loop, which is reversible by L-dopa.