Michel Rijntjes

Ventral and dorsal pathways for language

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.

Brain representation of active and passive movements

During active and passive (driven by a torque motor) flexion and extension of the right elbow, regional cerebral blood flow (rCBF) was measured in six healthy, male volunteers using positron emission tomography and the standard H2(15)O injection technique. During active as well as during passive movements of the right elbow there were strong increases in rCBF, identical in location, amount, and extent in the contralateral sensorimotor cortex. There were activations during both conditions in the supplementary motor area (stronger and more inferior in the active condition) and inferior parietal cortex (on the convexity during active movements and in the depth of the central sulcus during passive movements). During active movements only, activations of the basal ganglia and the cingulate gyrus were found. Brain activations during motor tasks are largely related to the processing of afferent information.

Experimental cranial pain elicited by capsaicin: a PET study

&NA; Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called ‘migraine generator’. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache.

Recovery of motor and language abilities after stroke: the contribution of functional imaging.

In recent years, functional imaging techniques, like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and transcranial magnetic stimulation (TMS), have shown that the improvement of motor and language function after ischemic stroke is accompanied by extensive reorganizational changes in the human cortex. To better understand these changes and to judge to what extent they could be responsible for clinical improvement, some basic principles of the organization of the motor and language system are discussed.Non-invasive functional imaging can have only a limited contribution in determining which of the possible underlying neural mechanisms, as they are known from animal experiments, play a role in functional recovery. However, they make it possible to define the functional consequences of anatomical lesions in individual patients and to correlate these functional consequences in the motor and language system with the clinical deficit. They can be used to assess the influence on the cortical reorganization of established and newer physiotherapies, logopedics and medical intervention, and they could be a useful tool in determining prognosis.

Structural Connectivity for Visuospatial Attention: Significance of Ventral Pathways

In the present study, we identified the most probable trajectories of point-to-point segregated connections between functional attentional centers using a combination of functional magnetic resonance imaging and a novel diffusion tensor imaging-based algorithm for pathway extraction. Cortical regions activated by a visuospatial attention task were subsequently used as seeds for probabilistic fiber tracking in 26 healthy subjects. Combining probability maps of frontal and temporoparietal regions yielded a network that consisted of dorsal and ventral connections. The dorsal connections linked temporoparietal cortex with the frontal eye field and area 44 of the inferior frontal gyrus (IFG). Traveling along superior longitudinal and arcuate fascicles, these fibers are well described in relation to spatial attention. However, the ventral connections, which traveled in the white matter between insula (INS) cortex and putamen parallel to the sylvian fissure, were not previously described for visuospatial attention. Linking temporoparietal cortex with anterior INS and area 45 of IFG, these connections may provide an anatomical substrate for crossmodal cortical integration needed for stimulus perception and response in relation to current intention. The newly anatomically described integral network for visuospatial attention might improve the understanding of spatial attention deficits after white matter lesions.

Neuroimaging in Stroke Recovery: A Position Paper from the First International Workshop on Neuroimaging and Stroke Recovery

Baron, Jean-Claude*Black, Sandra E.Butler, Andrew J.Carey, JamesChollet, FrancoisCohen, Leonardo G.*Corbetta, MaurizioCramer, Steven C.*Dobkin, Bruce H.*Frackowiak, RichardHeiss, W.D.Johansen-Berg, Heidi*Krakauer, John W.Lazar, Ronald M.Lennihan, Laura L.Loubinoux, Isabelle*Marshall, Randolph S.*Matthews, PaulMohr, J.P.Nelles, GereonPascual-Leone, AlvaroPomeroy, ValerieRijntjes, MichelRossini, Paolo MariaRothwell, John C.Seitz, Rudiger J.Small, Steven L.Sunderland, AlanWard, N.S.*Weiller, CorneliusWise, Richard J.S.IntroductionThe First International Workshop on Neuroimagingand Stroke Recovery was convened in February, 2004 inNew York City. The purpose of the workshop was to de-scribe the state of the field with regard to technical andanalytical methods, to discuss the use of complementaryimaging modalities, and to assess the current potential toapply functional neuroimaging to the development of ratio-nal treatment strategies for enhanced stroke recovery.Presented herein is a summary statement of topics dis-cussed at the workshop. These included (i) the clinical rel-evance of functional imaging changes after stroke for themotor and language systems; (ii) the technical challengesfaced in moving towards establishing functional neuro-imaging as a clinically useful tool; (iii) the contributions ofneurophysiological probes such as transcranial magnet-ic stimulation (TMS) to improve understanding of themechanisms underlying brain reorganization after stroke;and (iv) the potential role of neuroimaging in the assess-ment and development of rational pharmacological andbehavioral therapies.Clinical RelevanceFunctional recovery commonly occurs in survivingstroke patients in the weeks and months following theinjury. There is evidence from animal models that cere-bral reorganization underlies at least some of this recov-ery and it is hoped that an understanding of the neuro-physiological processes underlying this reorganization inthe human brain will lead to a rational approach to thetreatment of impairment. In animal models, focal braindamage triggers a number of changes at the molecular, cel-lular, and systems level, some of which alter the potentialfor cerebral reorganization and consequent functionalrecovery. Although the same techniques are not availableto study the working human brain, functional brain imag-ing has provided insights into how the human brainresponds to focal injury.

Multiple somatotopic representations in the human cerebellum

The classic view of representation in the cerebellum assumes two homunculi, one in the anterior lobe and one in the posterior lobe. Functional imaging has confirmed this somatotopy in the human anterior lobe but not, so far, in the posterior lobe. Using fMRI, we found separate peaks of activation for finger and toe in three ipsilateral cerebellar regions. In both the anterior and posterior lobe, the toe representation was semicircular around the finger area, with peaks of activation aligned in accord with the classic homunculi. Also, segregated peaks of activation were found in the pyramis vermis. These results confirm the existence of a second homunculus in the posterior lobe of the human cerebellum and suggest a third one.

Functional plasticity induced by mirror training: the mirror as the element connecting both hands to one hemisphere.

Background. Mirror therapy (MT) is a promising therapeutic approach in stroke patients with severe hand paresis. Objective. The ipsilateral (contralesional) primary sensorimotor cortex (SMC) and the mirror neuron system have been suggested to play decisive roles in the MT network. The present study investigated its underlying neural plasticity. Methods. Two groups of healthy participants (n = 13 in each group) performed standardized fine motor tasks moving pegs and marbles (20 min/d for 4 days) with their right hand with either a mirror (mirror training group, MG) or a nonreflective board (control training group, CG) positioned orthogonally in front of them. The number of items moved by each hand was tested after each training session. Functional MRI (fMRI) was acquired before and after the training procedure to investigate the mirror training (MTr)-specific network by the analysis of the factors Time and Group. Results. The hand performance test of the trained right hand did not differ between the 2 groups. The untrained left hand improved significantly more in the MG compared with the CG. fMRI analysis of action observation and imitation of grasping tasks demonstrated MTr-specific activation changes within the right dorsal and left ventral premotor cortex as well as in the left SMC (SMCleft). Analysis of functional and effective connectivity showed a MTr-specific increase of functional coupling between each premotor region and the left supplementary motor area, which in turn showed an increased functional interaction with the ipsilateral SMCleft. Conclusions. MTr remodels the motor system by functionally connecting hand movement to the ipsilateral SMC. On a system level, it leads to interference of the neural circuit related to motor programming and observation of the trained hand with the illusionary movement of the untrained hand.

[18F]FDG-PET is superior to [123I]IBZM-SPECT for the differential diagnosis of parkinsonism

Objective: Imaging of regional cerebral glucose metabolism with PET and striatal dopamine D2/D3 receptors (D2R) with SPECT improves the differential diagnosis of parkinsonism. We prospectively investigated 1) the diagnostic merits of these approaches in differentiating between Lewy body diseases (LBD; majority Parkinson disease [PD]) and atypical parkinsonian syndromes (APS); 2) the diagnostic value of [18F]fluorodeoxyglucose (FDG)-PET to differentiate among APS subgroups. Methods: Ninety-five of 107 consecutive patients with clinically suspected APS referred for imaging were recruited. [18F]FDG-PET scans were analyzed by visual assessment (including individual voxel-based statistical maps). Based on a priori defined disease-specific patterns, patients with putative APS were differentiated from LBD (first level) and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) (second level). [123I] iodobenzamide (IBZM)-SPECT datasets were subjected to an observer-independent regions-of-interest analysis to assess striatal D2R availability. Movement disorder specialists made final clinical diagnoses after a median follow-up time of 12 months. Results: Seventy-eight patients with clinically verified APS (n = 44) or LBD (n = 34) were included in the statistical analysis. The area under the receiver operating characteristic curve for discrimination between APS and LBD was significantly larger for [18F]FDG-PET (0.94) than for [123I]IBZM-SPECT (0.74; p = 0.0006). Sensitivity/specificity of [18F]FDG-PET for diagnosing APS was 86%/91%, respectively. Sensitivity/specificity of [18F]FDG-PET in identifying APS subgroups was 77%/97% for MSA, 74%/95% for PSP, and 75%/92% for CBD. Conclusions: The diagnostic accuracy of [18F]FDG-PET for discriminating LBD from APS is considerably higher than for [123I]IBZM-SPECT. [18F]FDG-PET reliably differentiates APS subgroups.

Learning, plasticity, and recovery in the central nervous system.

Abstract Cerebral functions can be described by the interaction of different brain regions as parts of distributed networks. Learning is seen as a refinement of the connection between the various parts of these networks. Plastic changes, as illustrated in brain charting techniques, are the result of learning (or use) in normal brains or found as adaptation (active or passive) after peripheral or central lesions. The relation between brain reorganization and recovery of function is investigated by two recent studies relating the training-induced improvement of lost function to changes in the brain. Others search for the effects of passive stimulation and drug influences. Independently of the approach, however, the general idea is that recovery can be seen as a reconnection between the remaining parts of the disturbed network.