Farsin Hamzei

Functional properties and interaction of the anterior and posterior intraparietal areas in humans

In the monkey the lateral bank of the anterior part of the intraparietal sulcus (area AIP), contains neurons that are involved in visually guided, object‐related hand movements. It has also been shown that neurons in the caudal part of the intraparietal sulcus (area CIP) preferentially respond to 3D surface orientation. According to these results, it has been hypothesized that neurons in area CIP primarily encode the 3D features of an object and forwards this information to area AIP. AIP then utilizes this information for appropriate hand actions towards the object. Based on analogies to these primate studies, recent neuroimaging studies have suggested human homologues of areas AIP and CIP, however, the functional interaction between these areas remains unclear. Our event related fMRI study was designed to address specifically the question, how CIP and AIP interact in the process of adjustment of hand orientation towards objects. Volunteers were asked to perform three tasks: discrimination of surface orientation, imaging of visually guided hand movements and execution of visually guided hand movements. Our data show that the human AIP was activated both during discrimination of surface orientation and during the subsequent spatial adjustment of the thumb and index finger position towards the surface orientation. In contrast, human CIP was activated by the surface orientation but not by spatial adjustment of finger position. These data clearly indicate that the function of human CIP is more involved in coding 3D features of the objects, whereas human AIP is more involved in visually guided hand movements, similar to its role in the monkey.

The influence of extra- and intracranial artery disease on the BOLD signal in FMRI

Functional MRI is based on the vascular response due to neuronal activation. The underlying mechanism of fMRI is the blood oxygenation level-dependent (BOLD) effect-a complex interplay between changes in the cerebral metabolisation rate of oxygen (CMRO2), neurovascular coupling, and the resulting hemodynamic response. An intact neurovascular coupling is essential for the detection of the BOLD signal and it seems likely that a disturbed cerebrovascular reserve capacity (CVRC) alters the BOLD response. We tested the hypothesis that extra- or intracranial artery disease influences the BOLD signal. Twenty-one patients with extra- or intracranial stenosis were studied with BOLD sensitive T2*-weighted MRI. All patients presented with transient or prolonged reversible ischemic symptoms ipsilateral to the artery disease but were asymptomatic at the time point of the MRI study. fMRI was performed employing a simple motor task (fist closure right and left). Additionally, the CVRC was assessed applying carbogen gas during serial T2*-weighted MRI for the calculation of CO(2) reactivity maps of the relative signal change. Signal differences between both hemispheres were compared in individual subjects and with healthy subjects. Patients with disturbed CVRC in the CO(2) reactivity maps showed either a significantly reduced (n = 5) or a negative (n = 1) BOLD signal in the affected compared to the unaffected primary sensorimotor cortex during fist closure. Patients with intact CVRC showed no significant BOLD signal differences between affected and unaffected hemisphere. Extra- or intracranial artery disease influences CVRC and consequently the BOLD signal. This observation is important for the clinical application of fMRI paradigms.

Negative dip in BOLD fMRI is caused by blood flow--oxygen consumption uncoupling in humans.

The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect.

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.

Visuomotor control within a distributed parieto-frontal network

The aim of this functional magnetic resonance imaging study was to investigate differences in visuomotor control with increasing task complexity. Twelve righthanded volunteers were asked to perform their signature under different degrees of visual control: internally generated movement with closed eyes, signing with open eyes, tracking the line of the projected signature forwards, and tracking the line of the projected signature backwards. There was a gradual onset and disappearance of activation within a distributed network. Parietal, lateral and medial frontal brain areas were activated during all conditions, confirming the involvement of a parietofrontal system. The weight of activation shifted with increasing task complexity. Internally generated movements activated predominantly the inferior parietal lobule and the ventral premotor cortex, as well as the rostral cingulate area, pre-supplementary motor area (pre-SMA) and SMA proper. Opening the eyes reduced SMA and cingulate activation and activated increasingly the occipito-parietal areas with higher task complexity. Visually guided movements produced an activation predominantly in the superior parietal lobule and dorsal premotor cortex. This study bridges human activation studies with the results of neurophysiological studies with monkeys. It confirms a gradual transition of visuomotor control with increasing task complexity within a distributed parietofrontal network.

Localization of human intraparietal areas AIP, CIP, and LIP using surface orientation and saccadic eye movement tasks

In monkeys, areas in the intraparietal sulcus (IPS) play a crucial role in visuospatial information processing. Despite many human neuroimaging studies, the location of the human functional homologs of some IPS areas is still a matter of debate. The aim of the present functional magnetic resonance imaging (fMRI) study was to identify the distinct locations of specific human IPS areas based on their functional properties using stimuli adapted from nonhuman primate experiments, in particular, surface orientation discrimination and memory guided saccadic eye movements (SEM). Intersubject anatomical variability likely accounts for much of the debate. By applying subject by subject analysis, we can demonstrate that sufficient intersubject anatomical and functional commonalities exist. Both the lateral bank of the anterior part of IPS, the putative human homolog of the area AIP, and the caudal part of the IPS (putative CIP) showed activation related to spatial discrimination of surface orientation. Eye tracking conducted during fMRI data acquisition allowed us to show that both areas were separated by an area related to SEM. This area was located in the middle region of the IPS (most probably including LIP), i.e., similar to the location observed in nonhuman primates. In 10 of 11 subjects our putative CIP activation was located in a medial side branch of the posterior part of the IPS, on the opposite side as described in nonhuman primates, making this landmark a useful anatomical marker for the location of CIP. Hum Brain Mapp 2008.

Age-independent activation in areas of the mirror neuron system during action observation and action imagery. A fMRI study

PURPOSE Recent studies have found age-related BOLD signal changes in several areas of the human brain. We investigated whether such changes also occur in brain areas involved in the processing of motor action observation and imagery. METHODS Functional magnetic resonance imaging with an experimental paradigm in which motor acts had to be observed and/or imagined from a first person perspective was performed in twenty-six subjects. RESULTS In line with previous work action observation and imagery induced BOLD signal increases in similar areas, predominantly in the premotor and parietal cortex. In contrast to young subjects the elderly displayed a stronger activity in most activated brain areas indicative of compensatory activity for the age-related decline of neural structures. Importantly, activity in the ventrolateral premotor cortex and inferior parietal cortex, seminal areas of the mirror neuron system, did not exhibit activity changes as a function of age. CONCLUSION These findings suggest that activity within the mirror neuron system is not age dependent and provide a neural basis for therapeutical interventions and novel rehabilitation treatments such as video therapy.

Individual Factors in Constraint-Induced Movement Therapy after Stroke

Objectives. Constraint-induced movement therapy (CIMT) has been shown to be effective in chronic stroke patients. It is worthwhile to investigate the influence of individual factors for two reasons: to find out whether they influence outcome and to see whether they support the theory underlying CIMT. Methods. Agroupof26 patients were treated with CIMT and followed over 6 months. In total, 14 individual factors were identified. Patients were assessed with 6 tests, including 2 commonly used after stroke (Frenchay Arm Test, 9 Hole Peg Test). Results. There were individual differences, but as a group, patients improved after therapy. There were no individual factors that influenced improvement in more than one test. Conclusions. CIMT is an effective therapy in patients with moderate impairment after stroke, also in tests commonly used in stroke rehabilitation. Factors that could have expected to make a difference on the basis of the theory behind CIMT (e.g., time since stroke, previous therapy, sensory deficit) did not influence results. Patients with hemorrhagic lesions and those with a high level of performance (Motor Activity Log > 2.5) profit as well. Pairwise therapy is as effective as individual therapy.

Structural and functional cortical abnormalities after upper limb amputation during childhood

Functional reorganization has been well documented in the human adult brain after amputation of the arm. To assess the effects of amputation on the developing brain, we investigated six patients with upper limb amputation in early childhood and one with right dysmelia. Transcranial magnetic stimulation indicated contralateral cortical disinhibition and enlargement of the excitable area of the stump. FMRI data corroborated these plastic changes and also showed an ipsilateral functional reorganization. In the T1-weighted MRI, we found structural deformities of the contralateral and ipsilateral central sulcus in three patients and a contralateral atrophic parietal lobule in two patients. Therefore, arm amputation in childhood affects functional organization as well as anatomical structure in both hemispheres.

Association of Activity Changes in the Primary Sensory Cortex With Successful Motor Rehabilitation of the Hand Following Stroke

Background. Previous studies demonstrated a posterior shift of activation toward the primary sensory cortex (S1) following stroke; however, any relationship between this posterior shift and clinical outcome measures for the affected hand function were unclear. Objective. The authors investigated the possible role of S1 in motor recovery. Methods. Assuming that previous studies examined inhomogeneous groups of patients, the authors selected participants with chronic stroke who had moderate hand paresis, normal sensory examination and somatosensory-evoked potentials, and no lesion within the S1, thalamus, or brain stem. Constraint-induced movement therapy (CIMT) was used to train the impaired hand. To relate fMRI (functional MRI) activation changes from baseline to post-CIMT, a correlation analysis was performed with changes of the Wolf Motor Function Test (WMFT) as a test for the hand function. Results. A close relationship was found between increases in hand function and peak changes in activation within the ipsilesional S1. With a better outcome, greater increases in activation within the S1 were evident (P < .03; r = 0.73). Conclusion. In selected patients, the sensory network influences training-induced motor gains. This predictive knowledge of plasticity when applying CIMT may suggest strategies to enhance the effect of therapy, such as the addition of electrical stimulation to enhance S1 excitability.