Assessment of cognitive functions before and after stereotactic interstitial radiosurgery of hypothalamic hamartomas in patients with gelastic seizures.

We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of (125)I-seed and 3 months after seed explantation. Performance was compared with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of (125)I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects.

Planning abilities and chess: a comparison of chess and non-chess players on the Tower of London task.

Playing chess requires problem-solving capacities in order to search through the chess problem space in an effective manner. Chess should thus require planning abilities for calculating many moves ahead. Therefore, we asked whether chess players are better problem solvers than non-chess players in a complex planning task. We compared planning performance between chess ( N=25) and non-chess players ( N=25) using a standard psychometric planning task, the Tower of London (ToL) test. We also assessed fluid intelligence (Raven Test), as well as verbal and visuospatial working memory. As expected, chess players showed better planning performance than non-chess players, an effect most strongly expressed in difficult problems. On the other hand, they showed longer planning and movement execution times, especially for incorrectly solved trials. No differences in fluid intelligence and verbal/visuospatial working memory were found between both groups. These findings indicate that better performance in chess players is associated with disproportionally longer solution times, although it remains to be investigated whether motivational or strategic differences account for this result.

Differential cerebral activation during observation of expressive gestures and motor acts.

We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (fMRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures.

Tracking the subprocesses of decision-based action in the human frontal lobes.

Situationally adaptive behavior relies on the identification of relevant target stimuli, the evaluation of these with respect to the current context and the selection of an appropriate action. We used functional magnetic resonance imaging (fMRI) to disentangle the neural networks underlying these processes within a single task. Our results show that activation of mid-ventrolateral prefrontal cortex (PFC) reflects the perceived presence of a target stimulus regardless of context, whereas context-appropriate evaluation is subserved by mid-dorsolateral PFC. Enhancing demands on response selection by means of response conflict activated a network of regions, all of which are directly connected to motor areas. On the midline, rostral anterior paracingulate cortex was found to link target detection and response selection by monitoring for the presence of behaviorally significant conditions. In summary, we provide new evidence for process-specific functional dissociations in the frontal lobes. In target-centered processing, target detection in the VLPFC is separable from contextual evaluation in the DLPFC. Response-centered processing in motor-associated regions occurs partly in parallel to these processes, which may enhance behavioral efficiency, but it may also lead to reaction time increases when an irrelevant response tendency is elicited.

What is in a name: comparing the Tower of London with one of its variants.

Since the implementation of the Tower of London (ToL) test by Shallice in 1982, numerous variants differing in the tower's physical appearance have been developed. Here we compare behavioral performance (n = 31) on the original Tower of London task consisting of three rods of unequal lengths with a three-ball version of the Ward and Allport Tower Task (1997) using three equally sized rods. In the problem set used, the start and goal states for both tower configurations were identical across all trials. The experiment was divided into two parts: in the first block, the problems presented were equalized with respect to the number of paths for achieving an optimal solution, the minimum number of moves, goal hierarchy, subgoaling patterns, and suboptimal alternatives between the two tower versions. As expected, participants showed the same performance scores for both types of towers when structural problem parameters were identical. In the second block, participants had to solve five-move problems which-due to the different rod sizes of the towers-had only one optimal solution in the original version, but two optimal solutions in the variant with three rods of equal length. Participants revealed lower performance scores and showed longer planning times in the original version than in the second tower version. These findings demonstrate that the two tower versions are only interchangeable when specific planning parameters are equalized. Otherwise, even if problems look identical, significant differences in performance may be found due to the differing problem spaces in the two tower versions.

The influence of sex differences and individual task performance on brain activation during planning.

Several studies have attempted to identify the neuronal basis of sex differences in cognition. However, group differences in cognitive ability rather than genuine neurocognitive differences between the sexes may account for their results. Here, we compare with functional magnetic resonance imaging the relation between gender, individual task performance, and planning-related brain activation. Men and women preselected to display identical performance scores showed a strong relation between individual task performance and activation of the right dorsolateral prefrontal and right inferior parietal cortex activation during a visuospatial planning task. No gender-specific activations were found. However, a different pattern emerged when subjects had to execute the motor responses to the problems. Better performance was associated with right dorsolateral prefrontal and right parahippocampal activations, and females exhibited a stronger right hippocampal activation than males. These findings underline that an individual's performance level rather than his or her sex largely determines the neuronal activation patterns during higher-level cognition.

Planning abilities and the Tower of London: is this task measuring a discrete cognitive function?

The Tower of London (ToL) test is widely used for measuring planning and aspects of problem solving. The primary focus of this study was to asses the relationship among different measures on the ToL. A secondary purpose was to examine the putative relationship between intelligence and working memory with that of ToL performance. Analyses of the interrelation of several ToL parameters indicated that better ToL performance was associated with longer preplanning time and shorter movement execution time. Good performers showed a stronger increase in preplanning duration with task difficulty then intermediate or poor planners. Stepwise multiple regression analysis yield fluid intelligence as the only significant predictor of ToL performance. These result suggest that the Tower of London assesses predominantly planning and problem solving and could not be explained by other cognitive domains.

When planning fails: individual differences and error-related brain activity in problem solving.

The neuronal processes underlying correct and erroneous problem solving were studied in strong and weak problem-solvers using functional magnetic resonance imaging (fMRI). During planning, the right dorsolateral prefrontal cortex was activated, and showed a linear relationship with the participants' performance level. A similar pattern emerged in right inferior parietal regions for all trials, and in anterior cingulate cortex for erroneously solved trials only. In the performance phase, when the pre-planned moves had to be executed by means of an fMRI-compatible computer mouse, the right dorsolateral prefrontal cortex was again activated jointly with right parahippocampal cortex, and displayed a similar positive relationship with the participants' performance level. Incorrectly solved problems elicited stronger bilateral prefrontal and left inferior parietal activations than correctly solved trials. For both individual ability and trial-specific performance, our results thus demonstrate the crucial involvement of right prefrontal cortex in efficient visuospatial planning.

The Tower of London: the impact of instructions, cueing, and learning on planning abilities.

The Tower of London (ToL) is a well-known test of planning ability, and commonly used for the purpose of neuropsychological assessment and cognitive research. Its widespread application has led to numerous versions differing in a number of respects. The present study addressed the question whether differences in instruction, cueing, and learning processes systematically influence ToL performance across five difficulty levels (three to seven moves). A total of 81 normal adults were examined in a mixed design with the between-subject factor instruction (online versus mental preplanning) and the within-subject factors cueing (cue versus non-cue test version) and learning processes (first block and second block). We also assessed general intelligence for further analyses of differences between instruction groups. In general, there was a significant main effect across the difficulty levels indicating that the rate of incorrect solutions increased with problem difficulty. The participants who were instructed to make full mental plans before beginning to execute movements (preplanning) solved significantly more problems than people who started immediately with task-related movements (online). As for the cueing conditions, participants with the minimum number of moves predetermined (cue) could solve more trials than people who were only instructed to solve the problems in as few moves as possible (non-cue). Participants generally increased performance in the second part of the test session. However, an interaction of presentation order of the cueing condition with learning indicated that people who started the tasks with the non-cue version showed significantly better performance in the following cue condition, while participants who started with the cue condition stayed at the same performance level for both versions. These findings suggest that instruction, cueing conditions, and learning processes are important determinants of ToL performance, and they stress the necessity of standardized application in research and clinical practice.

PET studies on the memory processing of word pairs in bilingual Finnish-English subjects.

This study examined the fundamental question whether verbal memory processing in two unrelated languages is mediated by a common neural system or by distinct cortical areas. Ten right-handed, male Finnish--English adult late bilinguals who had acquired the second language after the age of 10 were scanned whilst either encoding/retrieving word pairs in their mother tongue (Finnish) or in a foreign language (English). Within each language, subjects had to encode and retrieve four sets of 12 visually presented paired word associates which were not semantically related. Two sets consisted of highly imageable words (e.g. monkey-table; koira-lasi) and the other two sets of abstract word pairs (e.g. freedom-moral; uhka-suure). Presentation of pseudowords served as a reference condition. An emission scan was recorded after each intravenous administration of O-15 water. Encoding was associated with prefrontal and hippocampal activation. During memory retrieval, precuneus showed a consistent activation in both languages and for both highly imageable and abstract words. Although the brain mechanisms of the two languages share common components, differential activations were found in Broca's area and in the cerebellum as well as in the angular/supramarginal gyri according to the language used.

Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities.

In this study, we aimed to characterize commonalities and differences of activation patterns during verbal episodic memory processes across different presentation modalities (visual or auditory) and different imagery content (low or high) of the presented verbal memory items. Twelve right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol positron emission tomography scans. In six of the subjects the verbal material was presented visually, and in six subjects auditorily. The subjects had to encode and retrieve two sets of 12 word-pair associates of high (set 1) or low (set 2) imagery content (not semantically related). The presentation of nonsense words served as reference condition. Images were analyzed with statistical parametric mapping. Conjunction analysis was used to identify commonalities, and cognitive subtraction analysis was used to identify differences. The use of conjunction analyses enabled us to identify commonly activated regions involved in episodic encoding and retrieval of verbal material irrespective of the presentation modality or the imagery content. Our results add further evidence to recent findings that bilateral prefrontal activations are important for episodic retrieval and thus the role of the left prefrontal cortex has been underestimated during episodic retrieval. Furthermore, our results support the idea of functionally segregated areas in the prefrontal cortex. Finally, our results provide strong evidence that mesial parietal cortex (precuneus) involvement is not restricted to processes involving imagery.

Recognition and imitation of pantomimed motor acts after unilateral parietal and premotor lesions: a perspective on apraxia.

We compared gesture comprehension and imitation in patients with lesions in the left parietal lobe (LPAR, n=5) and premotor cortex/supplementary motor area (LPMA, n=8) in patients with damage to the right parietal lobe (RPAR, n=6) and right premotor/supplementary motor area (RPMA, n=6) and in 16 non-brain damaged control subjects. Three patients with left parietal lobe damage had aphasia. Subjects were shown 136 meaningful pantomimed motor acts on a videoscreen and were asked to identify the movements and to imitate the motor acts from memory with their ipsilesional and contralesional hand or with both hands simultaneously. Motor tasks included gestures without object use (e.g. to salute, to wave) pantomimed imitation of gestures on one's own body (e.g. to comb one's hair) and pantomimed imitation of motor acts which imply tool use to an object in extrapersonal space (e.g. to hammer a nail). Videotaped test performance was analysed by two independent raters; errors were classified as spatial errors, body part as object, parapraxic performance and non-identifiable movements. In addition, action discrimination was tested by evaluating whether a complex motor sequence was correctly performed. Results indicate that LPAR patients were most severely disturbed when imitation performance was assessed. Interestingly, LPAR patients were worse when imitating gestures on their own bodies than imitating movements with reference to an external object use with most pronounced deficits in the spatial domain. In contrast to imitation, comprehension was not or only slightly disturbed and no clear correlation was found between the severity of imitation deficits and gesture comprehension. Moreover, although the three patients with aphasia imitated the movements more poorly than non-aphasic LPAR patients, the severity of comprehension errors did not differ. Whereas unimanual imitating performance and gesture comprehension of PMA patients did not differ significantly from control subjects, bimanual tasks were severely disturbed, in particular when executing different movements simultaneously with the right and left hands.

[Comparison of PET and fMRI activation patterns durnig declarative memory processes]. / Vergleich von PET und fMRT-Aktivierungsmustern während deklarativer Gedächtnisvorgänge.

AIM: In this study neuronal correlates of encoding and retrieval in paired association learning were compared using two different neuroimaging methods: positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). METHODS: 6 right-handed normal male volunteers took part in the study. Each subject underwent six 0-15-butanol PET scans and on fMRI study comprising four single epochs on a different day. The subjects had to learn and retrieve 12 word pairs which were visually presented (highly imaginable words, not semantically related). RESULTS: Mean recall accuracy was 93% in the PET as well as in the fMRI experiment. During encoding and retrieval we found anterior cingulate cortex activation, and bilateral prefrontal cortex activation in both imaging modalities. Furthermore, we demonstrate the importance of the precuneus in episodic memory. With PET the results demonstrate frontopolar activations whereas fMRI fails to show activations in this area probably due to susceptibility artifacts. In fMRI we found additionally parahippocampal activation and due to the whole-brain coverage cerebellar activation during encoding. The distance between the center-of-mass activations in both modalities was 7.2 +/- 6.5 mm. CONCLUSION: There is a preponderance of commonalities in the activation patterns yielded with fMRI and PET. However, there are also important differences. The decision to choose one or the other neuroimaging modality should among other aspects depend on the study design (single subject vs. group study) and the task of interest.

Combined semantic dementia and apraxia in a patient with frontotemporal lobar degeneration.

In this study we report neuropsychological and brain-imaging findings in a patient with frontotemporal lobar degeneration. Brain imaging using registration of (18)fluorodeoxyglucose (FDG)-PET data to three-dimensional (3-D) magnetic resonance imaging showed atrophy and highly significant hypometabolism of the left temporal lobe and both frontal lobes. Volumetric measurements of the hippocampi/amygdala showed a reduction in volume of 25% on the left compared to right within cortical areas. Neuropsychological testing revealed semantic dementia with severe anomia as well as apraxia with impairment of both recognition and production of motor acts. The implications of this case of early manifestation of frontotemporal lobar degeneration for our knowledge of dementia are discussed.

Network analysis in episodic encoding and retrieval of word-pair associates: a PET study.

The involvement of distributed brain regions in declarative memory has been hypothesized based on studies with verbal memory tasks. To characterize episodic declarative memory function further, 14 right-handed volunteers performed a visual verbal learning task using paired word associates. The volunteers underwent positron emission tomography. 15O-butanol was used as a tracer of regional cerebral blood flow (rCBF). Inter-regional functional interactions were assessed based on within-task, across-subject inter-regional rCBF correlations. Anatomical connections between brain areas were based on known anatomy. Structural equation modelling was used to calculate the path coefficients representing the magnitudes of the functional influences of each area on the ones to which it is connected by anatomical pathways. The encoding and the retrieval network elicit similarities in a general manner but also differences. Strong functional linkages involving visual integration areas, parahippocampal regions, left precuneus and cingulate gyrus were found in both encoding and retrieval; the functional linkages between posterior regions and prefrontal regions were more closely linked during encoding, whereas functional linkages between the left parahippocampal region and posterior cingulate as well as extrastriate areas and posterior cingulate gyrus were stronger during retrieval. In conclusion, these findings support the idea of a global bihemispheric, asymmetric encoding/retrieval network subserving episodic declarative memory. Our results further underline the role of the precuneus in episodic memory, not only during retrieval but also during encoding.

Neuronal correlates of encoding and retrieval in episodic memory during a paired-word association learning task: a functional magnetic resonance imaging study.

The investigation of memory function using functional magnetic resonance imaging (fMRI) is an expanding field of research. The aim of this study was to demonstrate brain-activity patterns related to a word-pair association task employing a whole-brain EPI sequence. Six right-handed, healthy male volunteers (mean age: 27.5 years) took part in the study. fMRI was performed at a field strength of 1. 5 Tesla with 26-32 slices parallel to the AC-PC line, depending on individual brain size. Distributed brain regions were activated in episodic encoding and retrieval with similarities, but also (distinct) differences in activation patterns. Bilateral prefrontal cortical areas were involved when comparing encoding as well as retrieval to the reference condition (nonsense words). Furthermore, activation was observed in cerebellar areas during encoding, and activation in bilateral parietal areas (precuneus and inferior parietal cortex) was differentially more pronounced during retrieval. The activation of left dorsomedial thalamus during retrieval of high imagery-content word-pair associates may point to the role of this structure in episodic retrieval. The direct cognitive subtraction of encoding minus retrieval yielded a differentially larger left prefrontal activation. There was a differentially higher right prefrontal activation during retrieval than during encoding, underlining the proposed right/left asymmetry for episodic memory processes.

Episodic retrieval activates the precuneus irrespective of the imagery content of word pair associates. A PET study.

The aim of this study was to evaluate further the role of the precuneus in episodic memory retrieval. The specific hypothesis addressed was that the precuneus is involved in episodic memory retrieval irrespective of the imagery content. Two groups of six right-handed normal male volunteers took part in the study. Each subject underwent six [15O]butanol-PET scans. In each of the six trials, the memory task began with the injection of a bolus of 1500 MBq of [15O]butanol. For Group 1, 12 word pair associates were presented visually, for Group 2 auditorily. The subjects of each group had to learn and retrieve two sets of 12 word pairs each. One set consisted of highly imaginable words and another one of abstract words. Words of both sets were not related semantically, representing 'hard' associations. The presentations of nonsense words served as reference conditions. We demonstrate that the precuneus shows consistent activation during episodic memory retrieval. Precuneus activation occurred in visual and auditory presentation modalities and for both highly imaginable and abstract words. The present study therefore provides further evidence that the precuneus has a specific function in episodic memory retrieval as a multimodal association area.

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.

Encoding and retrieval in declarative learning: a positron emission tomography study.

We present neuroanatomical correlates of encoding and retrieval in an episodic memory task using visually presented highly imaginable word-pair associates. A total of 13 right-handed normal male volunteers took part in the study. Each subject underwent six (15)O-butanol PET scans. On each of the six trials the memory task began 30 s before the injection of a bolus of (15)O-butanol. The subjects had to learn and retrieve 12 word pairs (highly imaginable words, not semantically related, hard associations). The presentation of nonsense words served as a reference condition. Recall accuracy after 2-4 presentations was 66.1%+/-21.1 correct during the PET measurement so that scanning during the retrieval of word pair associates was appropriate to capture the brain activity associated with retrieval. The results obtained support the hypothesis of the presence of an asymmetric network consisting of distributed brain structures subserving associative memory. We show left dorsolateral prefrontal activation during the encoding of visually presented word pair associates, whereas retrieval led to bilateral frontal activation. Furthermore, the importance of the precuneus in the retrieval of highly imaginable word-pair associates using visual imagery as a mnemonic strategy is demonstrated.

[O-15-butanol Pet activation study on the cerebral representation of declarative memory]. / O-15-Butanol-PET-Aktivierungsstudie zur zerebralen Repräsentation deklarativer Gedächtnisvorgänge.

AIM: In this study, neuroanatomical correlates of encoding and retrieval in paired associate learning were evaluated with positron emission tomography using auditorily presented highly imaginable words. METHODS: Six right-handed normal male volunteers took part in the study. Each subject underwent six O-15-butanol PET scans. On each of the six trials the memory task began with the injection of a bolus of O-15-butanol. The subjects had to learn and retrieve twelve word pairs (highly imaginable words, not semantically related). The presentation of nonsense words served as reference condition. RESULTS: Recall accuracy after 2-4 presentations was high during the PET measurement. In both encoding and retrieval we found anterior cingulate activation. We show bilateral dorsolateral prefrontal activation during the encoding of auditorily presented word pair associates, whereas retrieval led to left frontal activation. Furthermore, we demonstrate the importance of the precuneus in the retrieval of highly imaginable word-pair associates. CONCLUSION: Our results support the hypothesis of the presence of distributed widespread brain structures subserving episodic declarative memory.