Biomedical subjects

F P Kolb

Publications and source records attributed to F P Kolb.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of the electrically evoked leg withdrawal reflex in cerebellar patients and healthy controls.

The aim of this study was to analyze the contribution of the cerebellum in the performance of the lower limb withdrawal reflexes. This has been accomplished by comparing the electrically evoked responses in cerebellar patients (CBL) with those in sex- and age-matched healthy control subjects (CTRL). The stimulus was applied to the subjects' medial plantar nerve in four blocks of ten trials each with switching the stimulus from one leg to the other after each block. Responses of the main muscle groups (tibial muscle: TA; gastrocnemius muscle: GA; rectus femoris muscle: RF; biceps femoris muscle: BI) of both legs were recorded during each stimulus. The group of CBL patients consisted of both focally lesioned patients (CBLf) and patients presenting a diffuse degenerative pathology (CBLd). (1) For the withdrawal reflex in CTRL subjects, responses were observed in distal and proximal muscles of the ipsilateral side and corresponding concomitant responses on the side contralateral to the stimulation, whereas in CBL patients responses were restricted primarily to distal muscles, particularly the TA of the ipsilateral, i.e. the stimulated, side. (2) The sequence of activation of the different distal and proximal muscles ipsilateral to the stimulation, derived from latencies and times-to-peak, was for the CTRL group: TA-GA-BI-RF. This sequence was found also in the CBLf patients on their unaffected side. However, on their affected side CBLf patients showed very early GA activation, almost simultaneously with TA and RF activations and before BI activation. RF activation before BI activation was also found in CBLd. In the latter group, GA was activated after RF but before BI with all responses typically delayed. (3) The general pattern of the electrically evoked lower limb reflex consisted of an early, excitatory F1 component and a later, excitatory F2 component of larger amplitude observed in the CTRL subjects and the CBLd patients. In contrast to this pattern CBLf patients exhibited large F1 components followed by small F2 components. (4) The characteristic differences in the withdrawal reflex responses of cerebellar patients depended on the type of the lesion, providing evidence for an important involvement of the cerebellum in the control of the performance of withdrawal reflexes.

Action Potentials↗

PubMed2005

Trace eyeblink conditioning in human subjects with cerebellar lesions.

Trace eyeblink conditioning was investigated in 31 patients with focal cerebellar lesions and 19 age-matched controls. Twelve patients presented with lesions including the territory of the superior cerebellar artery (SCA). In 19 patients lesions were restricted to the territory of the posterior inferior cerebellar artery (PICA). A 3D magnetic resonance imaging was used to determine the extent of the cortical lesion and possible involvement of cerebellar nuclei. Eyeblink conditioning was performed using a 40 ms tone as conditioned stimulus (CS) followed by a stimulus free trace-interval of 400 ms and a 100 ms air-puff as unconditioned stimulus (US). In SCA patients with lesions including parts of the cerebellar interposed nucleus trace eyeblink conditioning was significantly impaired. Pure cortical lesions of the superior cerebellum were not sufficient to reduce acquisition of trace conditioned eyeblink responses. PICA patients were not impaired in trace eyeblink conditioning. Consistent with animal studies the findings of the present human lesion study suggest that, in addition to forebrain areas, the interposed nucleus is of importance in trace eyeblink conditioning. Although cortical cerebellar areas appear less important in trace compared with delay eyeblink conditioning, the present data strengthen the view that cerebellar structures contribute to different forms of eyeblink conditioning paradigms.

Adult↗

PubMed2004

Eyeblink conditioning in patients with hereditary ataxia: a one-year follow-up study.

Delay eyeblink conditioning was examined in patients with genetically-defined heredoataxias and age-matched control subjects. 24 patients with spinocerebellar ataxia type 6 (SCA6), type 3 (SCA3), and Friedreich's ataxia (FRDA) participated. SCA6 affects primarily the cerebellum, whereas extracerebellar involvement is common in SCA3 and FRDA. Testing was performed in three sessions six months apart. Severity of ataxia was defined based on the International Ataxia Cooperative Rating Scale (ICARS). As expected, cerebellar patients were significantly impaired in eyeblink conditioning compared to controls. Signs of retention and further learning across sessions were present in controls, but not in the cerebellar patients. In addition, findings of disturbed timing of conditioned responses were observed. Both onsets and peaks of the conditioned responses (CRs) occurred significantly earlier in cerebellar patients. Shortened CR responses were most prominent in patients with primarily cerebellar cortical disease (SCA6). In the group of all cerebellar patients, the SCA3 and the FRDA group correlations between learning deficits and clinical findings were weak. Moderate-to-strong correlations were found in the SCA6 patients. There was no significant change, however, in clinical ataxia scores and CR incidence across the three sessions. In summary, impaired learning of conditioned eyeblink responses is a stable finding across multiple sessions in patients with degenerative cerebellar disorders. Eyeblink conditioning may be a useful measure of cerebellar impairment in patients with hereditary ataxias that primarily affect the cerebellum (such as SCA6). In other heredoataxias (such as SCA3 and FRDA), extracerebellar involvement not assessed by ICARS likely contributes to eyeblink conditioning abnormalities.

Adult↗

PubMed2004

Classically conditioned postural reflex in cerebellar patients.

The aim of the current study was to compare postural responses to repetitive platform-evoked perturbations in cerebellar patients with those of healthy subjects using a classical conditioning paradigm. The perturbations consisted of tilting of the platform (unconditioned stimulus: US) at random time intervals, preceded by an auditory signal that represented the conditioning stimulus (CS). Physiological reactions were recorded biomechanically by measuring the vertical ground forces, yielding the center of vertical pressure (CVP), and electrophysiologically by EMG measurements of the main muscle groups of both legs. The recording session consisted of a control section with US-alone trials, a testing section with paired stimuli and a brief final section with US-alone trials. Healthy control subjects were divided into those establishing conditioned responses (CR) in all muscles tested (strategy I) and those with CR in the gastrocnemius muscles only (strategy II), suggesting an associative motor-related process is involved. Patients with a diffuse, non-localized disease were almost unable to establish CR. This was also true for a patient with a focal surgical lesion with no CR on the affected side but who, simultaneously, showed an essentially normal CR incidence on the intact side. During US-alone trials healthy controls exhibited a remarkable decay of the UR amplitude due to a non-associative motor-related process such as habituation. The decay was most prominent in the paired trials section. In contrast, patients showed no significant differences in the UR amplitude throughout the entire recording session. Analysis of the CVP supported the electrophysiological findings, showing CR in the controls only. The differences between the responses of control subjects and those of the cerebellar patients imply strongly that the cerebellum is involved critically in controlling associative and non-associative motor-related processes.

Adult↗

PubMed2004

Amplitude changes of unconditioned eyeblink responses in patients with cerebellar lesions.

Timing and amplitude parameters of unconditioned eyeblink responses were investigated in 24 patients with unilateral cerebellar lesions following infarcts within the territory of the superior cerebellar artery (SCA, n=12) and of the posterior inferior cerebellar artery (PICA, n=12). The extent of cortical cerebellar lesions, i.e., which lobules were affected and possible involvement of cerebellar nuclei, was determined by three-dimensional magnetic resonance imaging (3D MRI). Amplitude parameters of eyeblink responses were normalized and expressed as percentage of the unaffected side in patients and the second tested side in age-matched controls. Normalized peak amplitudes, burst area and burst duration were significantly increased in SCA patients with lesions restricted to cortical areas. Burst onset and time to peak were not significantly different compared with controls. Temporal and amplitude parameters of eyeblink responses were unchanged in SCA patients with additional involvement of cerebellar nuclei and in patients with lesions of the PICA territory. Consistent with animal lesion and recording studies and a recent human functional magnetic resonance imaging (fMRI) study, the present data suggest that cortical areas of the superior cerebellum are of importance in eyeblink control in humans. These areas partly overlap with areas known to be critical in eyeblink conditioning.

Adult↗

PubMed2004

Use of sequence information in associative learning in control subjects and cerebellar patients.

Previous studies of our group have shown that cerebellar patients are impaired in their ability to associate a color and a numeral or two colors with a button push. The aim of the present study was to examine whether control subjects make use of sequence information in visuomotor associative learning tasks and if this ability is impaired in cerebellar patients. A group of eight patients with degenerative cerebellar disease and eight age, sex and IQ matched controls were tested. Subjects had to learn the association between pairs of colored squares and a button push. Two colored squares were shown one after the other in a fixed or random order on a computer screen. Control subjects but not cerebellar patients took advantage of the fixed order information of colored squares in order to improve associative learning. Differences between groups could not be explained by differences in verbal and visuospatial short-term memory, color discrimination, affective state or motor disturbances. Results suggest that impaired sequencing of sensory stimuli may contribute to disorders in visuomotor associative learning in cerebellar patients.

Adult↗

PubMed2003

Cerebellar responses evoked by nociceptive leg withdrawal reflex as revealed by event-related FMRI.

The aim of the present study was to examine nociceptive leg withdrawal reflex-related areas in the human cerebellum using event-related functional brain imaging (fMRI). Knowledge about cerebellar areas involved in unconditioned limb withdrawal reflex control has some relevance in understanding data of limb withdrawal reflex conditioning studies. Sixteen healthy adult subjects participated. Nociceptive leg withdrawal reflexes were evoked by electrical stimulation of the left tibial nerve behind the medial malleolus. An event-related fMRI paradigm was applied with a total of 30 stimuli being delivered pseudorandomly during 500 consecutive MR scans. Surface electromyographic (EMG) recordings were performed from the left anterior tibial muscle. Only trials with significant reflex EMG activity were used as active events in fMRI statistical analysis. The specified contrasts compared the active event condition with rest. Leg withdrawal reflex-related areas were located within the vermis, paravermis, and lateral posterior cerebellar hemispheres bilaterally. Vermal and paravermal areas in lobules III/IV in the anterior lobe and in lobule VIII in the posterior lobe agree with the cerebellar representation of climbing and mossy fiber hindlimb afferents and voluntary leg movements. They are likely related to efferent modulation of the leg withdrawal reflex and/or sensory processing of afferent inputs from the reflex and/or the noxious stimulus. Additional activation within vermal lobule VI and hemispheral lobules VI/Crus I may be related to other pain-related processes (e.g., facial grimacing, fear, and startlelike reactions).

Adult↗

PubMed2003

Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions.

The aim of the present study was to compare eyeblink conditioning in cerebellar patients with lesions including the territory of the superior cerebellar artery (SCA) and in patients with lesions restricted to the territory of the posterior inferior cerebellar artery (PICA). The cerebellar areas known to be most critical in eyeblink conditioning based on animal data (i.e. Larsell lobule H VI and interposed nucleus) are commonly supplied by the SCA. Eyeblink conditioning was expected to be impaired in SCA, but not in PICA patients. A total of 27 cerebellar patients and 25 age-matched controls were tested. Cerebellar lesions were primarily unilateral (n = 20). Most patients suffered from ischaemic infarctions of the SCA (n = 11) or the PICA (n = 13). The other patients presented with cerebellar tumours (n = 2) and cerebellar agenesis (n = 1). The extent of the cortical lesion (i.e. which lobuli were affected) and possible involvement of the cerebellar nuclei was determined by 3D-MRI. As expected, the ability to acquire classically conditioned eyeblink responses was significantly reduced in the group of all cerebellar patients compared with the controls. In the patients with unilateral cerebellar lesions, conditioning deficits were present ipsilaterally. In SCA patients with lesions including hemispheral lobules VI and Crus I, eyeblink conditioning was significantly reduced on the affected side compared with the unaffected side. No significant difference between the affected and unaffected sides was present in patients with lesions restricted to the common PICA territory (i.e. Crus II and below). Conditioning deficits were neither significantly different in SCA patients with pure cortical lesions compared with SCA patients with additional nuclear impairment nor in SCA patients with unilateral lesions compared with SCA patients with bilateral lesions. To summarize, unilateral cortical lesions of the superior cerebellum appear to be sufficient to reduce eyeblink conditioning in humans significantly.

Adult↗

PubMed2002

Classical conditioning of postural reflexes.

Unexpected external perturbations of body equilibrium elicit compensatory postural reflexes. The reflex patterns change only minimally, even after repetitive perturbations. This study addressed the question of whether classical conditioning can alter the reflex patterns. In the first session 27 healthy subjects were tested when standing on an unexpectedly tilting platform. Electromyographic (EMG) activity from different leg muscles and the vertical ground forces, from which the centre of vertical pressure (CVP) was computed, were recorded. In a subsequent session subjects were tested using the classical conditioning paradigm with the tilting platform as the unconditioned stimulus (US) and a prior auditory signal as the conditioning stimulus (CS). The decay of the unconditioned response (UR) observed in the first session was similar and small in all subjects. During conditioning, 22% of the subjects established conditioned responses (CR) in all muscles recorded (strategy 1). UR amplitudes of the anterior tibialis (TA) decayed more than in the first session. The resulting CVP excursions were similar to those observed in US-alone trials. The remaining subjects exhibited CR only in the gastrocnemius muscle but developed a substantial decay of UR, resulting in very small CVP excursions (strategy 2). Our data suggest that processing of US-preceding conditioning stimulus leads to different strategies in the control of postural adjustment with assumed underlying associative and non-associative plastic processes.

Adult↗

PubMed2002

MRI atlas of the human cerebellar nuclei.

The differential role of the cerebellar cortex and nuclei has rarely been addressed in human lesion and functional brain imaging studies. One important reason is the difficulty of defining the localization of the cerebellar nuclei and extent of possible lesions based on CT or MR scans. The present MRI investigation was specifically designed to study the anatomy of the deep cerebellar nuclei. In both basal ganglia and cerebellar nuclei of healthy human subjects the amount of iron is high compared to the rest of the brain. Clusters of iron are paramagnetic and, therefore, tend to cause local inhomogenities in a magnetic field. The iron-induced susceptibility artefacts were used to visualize the cerebellar nuclei as hypointensities on MR images. A three-dimensional atlas of the dentate (D), interposed (I), and fastigial (F) nuclei is presented in standard proportional stereotaxic space coordinates based on findings in a healthy 26-year-old female. A three-dimensional axial volume of the cerebellum was acquired using a T1-weighted fast low-angle shot (FLASH) sequence on a Siemens Sonata 1.5 Tesla MR. To increase the signal to noise ratio the sequence was acquired 5 times and averaged. Each volume was registered, resampled to 1.00 x 1.00 x 1.00-mm3 voxel size and spatially normalized into a standard proportional stereotaxic space (the MNI-space) using SPM99. Localization of cerebellar nuclei were confirmed by comparison with postmortem MRI and histological microsections of another brain.

Adult↗

PubMed2002

Motor deficits cannot explain impaired cognitive associative learning in cerebellar patients.

There is a strong evidence that the cerebellum is involved in associative motor learning. The exact role of the cerebellum in motor learning, and whether it is involved in cognitive learning processes too, are still controversially discussed topics. A common problem of assessing cognitive capabilities of cerebellar patients is the existence of additional motor demands in all cognitive tests. Even if the patients are able to cope well with the motor requirements of the task, their performance could still involve compensating strategies which cost them more attentional resources than the normal controls. To investigate such interaction effects of cognitive and motor demands in cerebellar patients, we conducted a cognitive associative learning paradigm and varied systematically the motor demands and the cognitive requirements of the task. Nine patients with isolated cerebellar disease and nine matched healthy controls had to learn the association between pairs of color squares, presented centrally on a computer monitor together with a left or right answer button. In the simple motor condition, the answer button had to be pressed once and in the difficult condition three times. We measured the decision times and evaluated the correctly named associations after the test was completed. The cerebellar subjects showed a learning deficit, compared to the normal controls. However, this deficit was independent of the motor difficulty of the task. The cerebellum seems to contribute to motor-independent processes, which are generally involved in associative learning.

Adult↗

PubMed2002

Fear conditioned changes of heart rate in patients with medial cerebellar lesions.

Fear conditioned changes of heart rate and skin conductance responses were investigated in patients with medial cerebellar lesions. A classical conditioning paradigm with a tone as the conditioned stimulus (CS) and an electrical shock as the unconditioned stimulus (US) was tested on five patients with medial cerebellar lesions due to surgery for astrocytoma and five controls. The CS preceded the US by 5900 ms and coterminated with the US. Changes in heart rate and skin conductance responses were obtained as measures for autonomic fear responses. Effects of conditioning were quantified by comparison of the habituation and extinction phases. Controls, but not cerebellar patients, showed a significant decrease of heart rate during fear conditioning. However, there were no significant fear conditioned changes in electrodermal responses in either group. In summary, the medial cerebellum seems to be involved in fear-conditioned bradycardia in humans.

Adolescent↗

PubMed2001

Changes in conditioned postural responses. Comparison between cerebellar patients and healthy subjects.

Postural responses elicited by external perturbation change characteristically during classical conditioning. This is assumed to be controlled by the cerebellum. In this study conditioning of postural responses in cerebellar patients was compared with that of healthy subjects. Subjects were tested when standing on a platform. Perturbations consisted of platform tilts (unconditioned stimulus, US), preceded by an auditory signal (conditioned stimulus, CS). The recording session consisted of US-alone and paired CS-US trials. In healthy subjects, unconditioned response (UR) amplitude decayed significantly with time in the recording session, especially strongly during paired trials. Amplitudes of cerebellar patients, however, decayed modestly and continuously, independently of the presence (paired trials) or otherwise of a CS. In addition, only healthy subjects established conditioned responses. Our data suggest that the prior auditory information is used to prepare postural responses. Deficits in cerebellar patients suggest a possible role of the cerebellum in controlling this plastic motor-related process.

Acoustic Stimulation↗

PubMed2000

A possible role of the human cerebellum in conditioning of the jaw-opening reflex.

The role of the human cerebellum in classical conditioning of the jaw-opening reflex was investigated using positron emission tomography (PET) in healthy subjects. The jaw-opening reflex was elicited by electrical stimulation of the right corner of the mouth (unconditioned stimulus, US). The conditioned stimulus was a tone preceding the US and coterminating with the US. Changes of regional cerebral blood flow (rCBF) were correlated with the rate of conditioning per PET scan. Conditioning effects were present in one third of all subjects. In these subjects, a significant increase of rCBF in the ipsilateral, intermediate cerebellum was shown during ongoing conditioning. Thus, the intermediate cerebellum appears to be involved in classical conditioning of the jaw-opening reflex in humans.

Adult↗

PubMed2000

Involvement of the human medial cerebellum in long-term habituation of the acoustic startle response.

Animal studies have shown an involvement of the cerebellar vermis in long-term habituation of the acoustic startle response, but not in short-term habituation. The aim of the present study was to investigate whether short-term and long-term habituation of the acoustic startle response are impaired in patients with medial cerebellar lesions. Five patients with midline cerebellar lesions due to surgery for astrocytoma and ten healthy, age- and sex-matched subjects were studied. Subjects received 40 acoustic startle stimuli each day on five successive days. Peak amplitudes of the startle response recorded at the orbicularis oculi and the sternomastoid muscles were obtained. Data were analyzed for response decrement within the training session of one day (short-term habituation) and for a decrease in the startle response across the five training days (long-term habituation). Short- and long-term habituation of the startle response recorded at the sternomastoid muscles could be achieved in controls and in cerebellar patients. However, long-term habituation of the blink component of the acoustic startle response recorded at the orbicularis oculi muscles was significantly impaired in patients with cerebellar lesions compared with control subjects, whereas short-term habituation was preserved in both groups. The present findings suggest that the medial cerebellum is involved in long-term habituation of the blink component of the startle response in humans.

Adolescent↗

PubMed2000

Classically conditioned withdrawal reflex in cerebellar patients. 1. Impaired conditioned responses.

The role of the cerebellum in the classically conditioned, human lower-limb-withdrawal reflex was studied in ten patients with pure cerebellar diseases (CBL), ten patients showing additional extracerebellar symptoms (CBL+), and in 11 sex- and age-matched normal controls (CTRL). Where conditioning was successful, the electrically evoked, unconditioned response was preceded by a tone-conditioned response (CR). CR incidence was variable, with best results in the CTRL, significantly less in CBL, and lowest in CBL+. Although CRs could be established in subjects in all groups, a continuous increase in the CR incidence in the course of the recording session was observed primarily in CTRL. In CBL and CBL+, such a characteristic reflex acquisition was rather the exception. CR onsets in CBL were within the range of those in CTRL, but CR amplitude was significantly lower in CBL. Cerebellar patients with circumscribed lesions behaved differently in our motor-learning paradigm, depending on the lesion site. Patients suffering from pathology of the posterior inferior cerebellum showed a mean CR incidence within the lower range of CTRL. In contrast, if the anterior and superior cerebellum was affected, few or even no CRs were observed. Our findings thus provide evidence that the human cerebellum is required for the acquisition and the retention of this specific conditioned limb-withdrawal reflex. In particular, anterior and superior parts of the cerebellum appear to be involved. Thus, an expansion of the current concept of clinically based, functional compartmentalization is suggested, such that anterior and superior cerebellar regions must be intact to establish plastic changes required for the acquisition of the conditioned withdrawal response.

Adult↗

PubMed2000

Classically conditioned withdrawal reflex in cerebellar patients. 2. Impaired unconditioned responses.

The study addresses the issue of the role of the cerebellum in human withdrawal-reflex conditioning by comparing data from patients with pure cerebellar diseases (CBL, n = 10) and from cerebellar patients showing additional extracerebellar symptoms (CBL+, n = 10) with those from 11 control subjects (CTRL). During recording sessions, the standard delay-conditioning paradigm with paired-trials was used with tone as the conditioned stimulus (CS). Parameters of the conditioned muscle responses are analyzed in an accompanying paper. Here, we focus on the unconditioned muscle response. A train of current pulses (unconditioned stimulus, US) evoked a lower-limb withdrawal reflex (unconditioned response, UR), which was recorded electromyographically from leg muscles. During the recording sessions with CTRL subjects, UR amplitudes decayed from initially 100% to approximately 50% at the end of the session. This type of decay was clearly less pronounced in the CBL group and minimal in the CBL+ group. Furthermore, the CBL group exhibited UR onsets that were delayed by 20 ms compared with those from CTRL subjects. Although the ranges of measurements characterizing the URs of a given cerebellar patient tested in the paired-trial paradigm overlapped with those of control subjects, the statistically significant differences observed at the group level suggest deficits in the performance of the reflex responses. The delayed URs in patients and the different type of decay of UR amplitudes in repetitively evoked withdrawal reflexes constitute evidence that the cerebellum is critically involved in the control of these UR parameters.

Adult↗

PubMed2000

Fear conditioned potentiation of the acoustic blink reflex in patients with cerebellar lesions.

OBJECTIVE: To investigate whether the human cerebellum takes part in fear conditioned potentiation of the acoustic blink reflex. METHODS: A group of 10 cerebellar patients (eight patients with lesions involving the medial cerebellum, two patients with circumscribed lesions of the cerebellar hemispheres) was compared with a group of 16 age and sex matched healthy control subjects. The fear conditioned potentiation paradigm consisted of three phases. During the first, habituation phase subjects received 20 successive acoustic blink stimuli. In the subsequent fear conditioning phase, subjects passed through 20 paired presentations of the unconditioned fear stimulus (US; an electric shock) and the conditioned stimulus (CS; a light). Thereafter, subjects underwent the potentiation phase, which consisted of a pseudorandom order of 12 trials of the acoustic blink stimulus alone, 12 acoustic blink stimuli paired with the conditioned stimulus, and six conditioned stimuli paired with the unconditioned stimulus. The EMG of the acoustic blink reflex was recorded at the orbicularis oculi muscles. The potentiation effect was determined as the difference in normalised peak amplitude of the blink reflex evoked by pairs of CS and acoustic blink stimuli and evoked by the acoustic stimulus alone. RESULTS: In the habituation phase, short term habituation of the acoustic blink reflex was preserved in all cerebellar patients. However, in the potentiation phase, the potentiation effect of the blink reflex was significantly reduced in patients with medial cerebellar lesions compared with the controls (mean (SD) potentiation effect (%), patients: -6.4 (15.3), controls: 21.6 (35.6)), but was within normal limits in the two patients with lateral lesions. CONCLUSIONS: The present findings suggest that the human medial cerebellum is involved in associative learning of non-specific aversive reactions-that is, the fear conditioned potentiation of the acoustic blink reflex.

Adolescent↗