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Biomedical subjects

H J Freund

Publications and source records attributed to H J Freund.

At least 55 records · Page 3Linked to original sources

A parieto-premotor network for object manipulation: evidence from neuroimaging.

Functional magnetic resonance imaging (fMRI) was used to assess cerebral activation during manipulation of various complex meaningless objects as compared to manipulation of a single simple object (a sphere). Significant activation was found bilaterally in the ventral premotor cortex (Brodmann's area 44), in the cortex lining the anterior part of the intraparietal sulcus (most probably corresponding to monkey anterior intraparietal area, AIP), in the superior parietal lobule and in the opercular parietal cortex including the secondary somatosensory area (SII). We suggest that the cortex lining the anterior part of the intraparietal sulcus and area 44 are functionally connected and mediate object manipulation in humans.

Adult↗

Cerebral midline structures in bimanual coordination.

In six healthy right-handed volunteers, we compared the cerebral activation pattern related to unimanual right- and left-hand movements and to bimanual in-phase and anti-phase movements using functional magnetic resonance imaging (fMRI). Internally paced unimanual finger-to-thumb opposition movements led to a strong contralateral activation of primary sensorimotor areas in all six subjects. Midline activity was lateralized to the left side during right-hand movements, but to both sides during left-hand movements. Activity patterns of bimanual in-phase movements resembled the combined activity patterns of the two unimanual conditions: right and left hemispheric activations of the primary sensorimotor cortices and predominantly left-sided medial frontal activity. In contrast, during anti-phase movements, we observed a clear increase in activity, in both right and left frontal midline areas and in right hemispheric, mainly dorsolateral premotor areas compared to in-phase movements. These results indicate that frontal midline activity is not specific for bimanual movements per se. It can already be involved during simple unimanual movements but becomes progressively more involved during more complex aspects of movement control.

Adult↗

Pain affect without pain sensation in a patient with a postcentral lesion.

We report findings from clinical examination and cutaneous laser stimulation in a 57-year-old male, who suffered from a right-sided postcentral stroke. In this patient, we were able to demonstrate (i) a dissociation of discriminative and affective components of pain perception and, for the first time in humans, (ii) the dependence of sensory-discriminative pain component and first pain sensation on the integrity of the lateral pain system.

Affect↗

Cortical activation during oesophageal stimulation: a neuromagnetic study.

We investigated the neuromagnetic responses to mechanical stimulation of the oesophagus. In six healthy right-handed volunteers (mean age 31.6 years) the proximal and distal oesophagus were stimulated by electronically controlled pump-inflation of a silicone balloon once every 4.5-5.5 sec (dwell time 145 msec). The balloon volume was adjusted to induce different sensation levels (i) just above threshold of perception, (ii) strong sensation and (iii) painful sensation. Evoked magnetic brain responses were recorded time-locked to stimulus onset with a Neuromag-122TM whole-head neuromagnetometer and modelled as equivalent current diploe (ECD) sources. ECDs were superimposed on individual magnetic resonance imaging (MRI) scans. Magnetic brain responses following distal oesophageal stimulation were adequately explained by a time-varying 2-4 dipole model with unilateral or bilateral sources in second somatosensory cortex and later sources in the frontal cortex. With increasing stimulus intensities, latencies of the sources decreased and amplitudes increased. Proximal oesophageal stimulation led to activation of source areas spatially similar to those of distal oesophageal stimulation but with shorter response latencies. Both painful and nonpainful mechanical stimulation of the oesophagus activate the second somatosensory cortex (SII). Evidence for topographic organization of oesophageal afferents in SII is poor.

Adult↗

Different cortical organization of visceral and somatic sensation in humans.

Sensory stimuli from the visceral domain exhibit perceptual characteristics different from stimuli applied to the body surface. Compared with somatosensation there is not much known about the cortical projection and functional organization of visceral sensation in humans. In this study, we determined the cortical areas activated by non-painful electrical stimulation of visceral afferents in the distal oesophagus, and somatosensory afferents in the median nerve and the lip in seven healthy volunteers using whole-head magnetoencephalography. Stimulation of somatosensory afferents elicited short-latency responses (approximately 20-60 ms) in the primary somatosensory cortex (SI) contralateral (median nerve) or bilateral (lip) to the stimulated side, and long-latency responses (approximately 60-160 ms) bilaterally in the second somatosensory cortex (SII). In contrast, stimulation of visceral oesophageal afferents did not evoke discernible responses in SI but well reproducible bilateral SII responses (approximately 70-190 ms) in close vicinity to long-latency SII responses following median nerve and lip stimuli. Psychophysically, temporal discrimination of successive stimuli became worse with increasing stimulus repetition rates (0.25 Hz, 0.5 Hz, 1 Hz, 2 Hz) only for visceral oesophageal, but not for somatosensory median nerve stimuli. Correspondingly, amplitudes of the first cortical response to oesophageal stimulation emerging in the SII cortex declined with increasing stimulus repetition rates whereas the earliest cortical response elicited by median nerve stimuli (20 ms SI response) remained unaffected by the stimulus frequency. Our results indicate that visceral afferents from the oesophagus primarily project to the SII cortex and, unlike somatosensory afferents, lack a significant SI representation. We propose that this cortical projection pattern forms the neurophysiological basis of the low temporal and spatial resolution of conscious visceral sensation.

Adult↗

The role of ventral medial wall motor areas in bimanual co-ordination. A combined lesion and activation study.

Two patients with midline tumours and disturbances of bimanual co-ordination as the presenting symptoms were examined. Both reported difficulties whenever the two hands had to act together simultaneously, whereas they had no problems with unimanual dexterity or the use of both hands sequentially. In the first patient the lesion was confined to the cingulate gyrus; in the second it also invaded the corpus callosum and the supplementary motor area. Kinematic analysis of bimanual in-phase and anti-phase movements revealed an impairment of both the temporal adjustment between the hands and the independence of movements between the two hands. A functional imaging study in six volunteers, who performed the same bimanual in-phase and anti-phase tasks, showed strong activations of midline areas including the cingulate and ventral supplementary motor area. The prominent activation of the ventral medial wall motor areas in the volunteers in conjunction with the bimanual co-ordination disorder in the two patients with lesions compromising their function is evidence for their pivotal role in bimanual co-ordination.

Adult↗

Parallel activation of primary and secondary somatosensory cortices in human pain processing.

Cerebral processing of pain has been shown to involve primary (SI) and secondary (SII) somatosensory cortices. However, the temporal activation pattern of these cortices in nociceptive processing has not been demonstrated so far. We therefore used whole-head magnetoencephalography to record cortical responses to cutaneous laser stimuli in six healthy human subjects. By using selective nociceptive stimuli our results confirm involvement of contralateral SI and bilateral SII in human pain processing. Beyond they show for the first time simultaneous activation onset of contralateral SI and SII after approximately 130 ms, indicating parallel thalamocortical distribution of nociceptive information. This contrasts to the serial cortical organization of tactile processing in higher primates and instead corresponds to the parallel cortical organization in lower primates and nonprimates. Thus our finding suggests preservation of the basic mammalian parallel organizational scheme in human pain processing, whereas in the tactile modality parallel organization appears to be abandoned in favor of a serial processing scheme. Functionally, preservation of direct access to SII underscores the relevance of this area in human pain processing, probably reflecting an important role of SII in nociceptive learning and memory.

Adult↗

Diffusion- and perfusion-weighted MRI. The DWI/PWI mismatch region in acute stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are relatively new MR techniques increasingly used in acute stroke. During the first hours of stroke evolution, the regions with abnormal perfusion are typically larger than the DWI lesions, and this mismatch region has been suggested to be "tissue at risk." The aim of this study was to evaluate the PWI/DWI mismatch region in acute stroke patients and find parameters indicative of both infarct progression and functional impairment. METHODS: Twenty patients with nonlacunar ischemic stroke were imaged with DWI, PWI, and conventional MRI within 24 hours of symptom onset and after 1 week; in addition, the European Stroke Scale (ESS) score was recorded. With PWI, the volumes of regions with "time-to-peak" (TTP) delays of >/=2, 4, 6, 8, and 10 seconds were measured; these volumes were compared with the acute DWI lesion volumes, final infarct size, and ESS score. RESULTS: In 80% of patients the acute DWI lesion was surrounded by regions with abnormal TTP delays (PWI>DWI lesion). A TTP delay of >/=6 s in the mismatch region was found to be associated with lesion enlargement between the initial and follow-up MRI scans. Lesions increased in 9 of 12 patients (75%) in whom the area with TTP delay >/=6 s was larger than the DWI lesion, but they increased in only 1 of 8 (12.5%) of the remaining patients, in whom the area with a TTP delay >/=6 s was smaller than the DWI lesion. The volume of the regions with TTP delays of >/=4 s correlated better with ESS (r=-0.88, P<0.001) than other PWI (or DWI) volumes, which indicated that a TTP delay of approximately 4 s might be the threshold for functional impairment of brain tissue. CONCLUSIONS: Only patients with severe perfusion deficits in the PWI/DWI mismatch (TTP delays of >/=6 s) are at high risk of lesion enlargement. Functionally, more moderate perfusion deficits (TTP delays >/=4 and <6 s) appear to also contribute to the acute clinical deficit.

Acute Disease↗

The role of diaschisis in stroke recovery.

BACKGROUND AND PURPOSE: Recovery from hemiparesis after stroke has been shown to involve reorganization in motor and premotor cortical areas. However, whether poststroke recovery also depends on changes in remote brain structures, ie, diaschisis, is as yet unresolved. To address this question, we studied regional cerebral blood flow in 7 patients (mean+/-SD age, 54+/-8 years) after their first hemiparetic stroke. METHODS: We analyzed imaging data voxel by voxel using a principal component analysis by which coherent changes in functional networks could be disclosed. Performance was assessed by a motor score and by the finger movement rate during the regional cerebral blood flow measurements. RESULTS: The patients had recovered (P<0. 001) from severe hemiparesis after on average 6 months and were able to perform sequential finger movements with the recovered hand. Regional cerebral blood flow at rest differentiated patients and controls (P<0.05) by a network that was affected by the stroke lesion. During blindfolded performance of sequential finger movements, patients were differentiated from controls (P<0.05) by a recovery-related network and a movement-control network. These networks were spatially incongruent, involving motor, sensory, and visual cortex of both cerebral hemispheres, the basal ganglia, thalamus, and cerebellum. The lesion-affected and recovery-related networks overlapped in the contralesional thalamus and extrastriate occipital cortex. CONCLUSIONS: Motor recovery after hemiparetic brain infarction is subserved by brain structures in locations remote from the stroke lesion. The topographic overlap of the lesion-affected and recovery-related networks suggests that diaschisis may play a critical role in stroke recovery.

Adult↗

Interaction of finger representation in the human first somatosensory cortex: a neuromagnetic study.

Neuromagnetic responses to separate tactile stimulation of digits I, II and V and simultaneous stimulation of digit pairs II and I, and II and V, were recorded in six healthy adult subjects using a 122-channel whole-head neuromagnetometer in order to investigate functional overlap of finger representations in primary somatosensory cortex (SI). Evoked responses to single digit stimulation were explained by time-varying equivalent current dipoles (ECDs) located in SI. These ECDs were then used to explain responses to stimulation of digit pairs. A cortical interaction ratio (IR) was defined as the vector sum of peak source amplitudes to separate stimulations of two fingers divided by the vector sum of source amplitudes to simultaneous stimulation of the two digits. Mean IR was significantly higher (P<0.05; Wilcoxon test) for digit pair II + I (1.69+/- 0.15) compared to digit pair II + V (1.14+/- 0.12). These results indicate that there is an overlap of finger representations in human SI which differs between anatomically adjacent and non-adjacent digit pairs.

Adult↗

Functional organization of the auditory cortex is different in stutterers and fluent speakers.

Impaired auditory feedback has been suggested to cause stuttering, and subtle irregularities of audition have been reported in behavioural studies. To characterize processing at the auditory cortical level, we recorded neuromagnetic responses to monaural tones in nine stutterers and 10 fluent speakers while the subjects were reading silently, with mouth movements only, aloud, and in chorus with another person. The basic functional organization of the auditory cortices was found to be different in stutterers and controls. The altered interhemispheric balance in stutterers was affected by speech production, due to changes in the left auditory cortical representation, and more severely by self-paced than accompanied speech. This may lead to transient non-optimal interpretation of the auditory input and affect speech fluency.

Adult↗

Early-onset multisystem degeneration with central motor, autonomic and optic nerve disturbances: unusual Riley-Day syndrome or new clinical entity?

We report a 21-year-old woman presenting with a slowly progressive tetraparesis, optic nerve atrophy on both sides, and autonomic disturbances since early childhood. The patient has been carefully followed up for 5 years with clinical and ancillary investigations. The results and the time course strongly suggest an underlying degenerative syndrome affecting parts of three major systems: autonomic, motor and visual. Some symptoms resemble familial dysautonomia (FD, Riley-Day syndrome), however, hallmarks of FD, such as absence of fungiform papillae of the tongue, abnormal reaction on intradermal histamine injection, absent tendon reflexes, are missing, and central motor disturbances have not been described in FD. We consider this syndrome a slowly progressive multisystemic degeneration with two unusual hitherto unreported features: the combination of affected systems (autonomic and motor systems, optic nerves), and the early onset.

Adult↗

Role of the premotor cortex in recovery from middle cerebral artery infarction.

OBJECTIVE: To study the mechanisms underlying recovery from middle cerebral artery infarction in 7 patients with an average age of 53 years who showed marked recovery of hand function after acute severe hemiparesis caused by their first-ever stroke. INTERVENTIONS: Assessment of motor functions, transcranial magnetic stimulation, somatosensory evoked potentials, magnetic resonance imaging, and positron emission tomographic measurements of regional cerebral blood flow during finger movement activity. RESULTS: The infarctions involved the cerebral convexity along the central sulcus from the Sylvian fissure up to the hand area but spared the caudate nucleus, thalamus, middle and posterior portions of the internal capsule, and the dorsal part of the precentral gyrus in each patient. After recovery (and increase in motor function score of 57%, P<.001), the motor evoked potentials in the hand and leg muscles contralateral to the infarctions were normal, whereas the somatosensory evoked potentials from the contralateral median nerve were reduced. During fractionated finger movements of the recovered hand, regional cerebral blood flow increases occurred bilaterally in the dorsolateral and medial premotor areas but not in the sensorimotor cortex of either hemisphere. CONCLUSIONS: Motor recovery after cortical infarction in the middle cerebral artery territory appears to rely on activation of premotor cortical areas of both cerebral hemispheres. Thereby, short-term output from motor cortex is likely to be initiated.

Adult↗

Increased long-term potentiation in the surround of experimentally induced focal cortical infarction.

Functional recovery after stroke is partly due to cortical reorganization on a structural as well as a functional level. Recent investigations have shown that the excitability of brain areas surrounding cortical ischemic lesions is increased, probably due to a down-regulation of gamma-aminobutyric acid-receptor activity. There is some evidence that these changes might increase the susceptibility of the lesioned brain for adaptive changes and recovery. Here, we investigated the propensity for the induction of long-term potentiation (LTP) in the surround of experimentally induced focal cortical infarcts in rat somatosensory cortex in vitro. By using standard paradigms, LTP induction was found to be facilitated ipsilaterally in slices of lesioned animals 1 week after lesion induction. In homotopic contralateral areas, LTP was not different from control values. As LTP is commonly associated with plasticity and learning, the results provide further evidence for the lesion-induced amplification of network plasticity, as it is required for the reshaping of cortical circuits by timely training procedures.

Animals↗

Somatic and limbic cortex activation in esophageal distention: a functional magnetic resonance imaging study.

Little is known about the cerebral representations of visceral sensations in humans. Using functional magnetic resonance imaging (fMRI), we mapped the cortical areas of the human brain that were activated by mechanical stimulation of the esophagus in 5 healthy volunteers. Stimulation probes were placed into the distal part of the esophagus and inflated to produce a local distention. The cerebral activation pattern was related to the strength and quality of the stimulus. The weakest stimulus accompanied by a well-localized albeit weak retrosternal sensation activated only the parietal opercular cortices, probably including the secondary somatosensory cortex (SII). Additional activation of the primary sensorimotor cortex (SI) at the level of the face and mouth representation as well as of the right premotor cortex was found during repetitive distention of the esophagus at 0.5 Hz. Repetitive stimulation at 1 Hz additionally activated the insula bilaterally. The strongest distention stimulus, which caused a painful retrosternal sensation, resulted in an activation of the anterior cingulate cortex. Our findings demonstrate that SII is the primary cortical target of visceral afferents originating in the esophagus. Limbic structures become engaged when the visceral sensation is unpleasant or painful.

Adult↗

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease.

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1+/-14.8 to 23.9+/-11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n=6), 9 months (n=6), and 12 months (n=4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for "off" symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.

Adult↗

Force regulation is deficient in patients with parietal lesions: a system-analytic approach.

By means of a quantitative system-analytic investigation strategy, the postural motor control of the fingers was evaluated, to characterise the possible deficit of force regulation in patients with parietal lesions. In spite of a normal response to short torque pulses, the parietal-lesion patients had difficulties in returning to the preload level after the application of an additional step torque load to fingers II-IV of their left or right hands. The control offset (measured 500 ms after step torque application) was significantly larger in the patient group. This deficit in the investigated patients with parietal lesions to compensate for step torque loads was not due to a paresis, but rather resulted from a disturbance in the generation of a sufficient counterforce against the applied step torque within an adequate time window and motor pattern. This distinct force-regulation deficit was found in patients with left- and right-sided parietal lesions.

Adult↗