B.J. Krause

Modulation of the neuronal circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation

We studied the effect of repetitive transcranial magnetic stimulation (rTMS) on changes in regional cerebral blood flow (rCBF) as revealed by positron emission tomography (PET) while subjects performed a 2-back verbal working memory (WM) task. rTMS to the right or left dorsolateral prefrontal cortex (DLPFC), but not to the midline frontal cortex, significantly worsened performance in the WM task while inducing significant reductions in rCBF at the stimulation site and in distant brain regions. These results for the first time demonstrate the ability of rTMS to produce temporary functional lesions in elements of a neuronal network thus changing its distributed activations and resulting in behavioral consequences.

Dissociating neural correlates for nouns and verbs

Dissociations in the ability to produce words of different grammatical categories are well established in neuropsychology but have not been corroborated fully with evidence from brain imaging. Here we report on a PET study designed to reveal the anatomical correlates of grammatical processes involving nouns and verbs. German-speaking subjects were asked to produce either plural and singular nouns, or first-person plural and singular verbs. Verbs, relative to nouns, activated a left frontal cortical network, while the opposite contrast (nouns-verbs) showed greater activation in temporal regions bilaterally. Similar patterns emerged when subjects performed the task with pseudowords used as nouns or as verbs. These results converge with findings from lesion studies and suggest that grammatical category is an important dimension of organization for knowledge of language in the brain.

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.

Chronometry of parietal and prefrontal activations in verbal working memory revealed by transcranial magnetic stimulation

We explored the temporal dynamics of parietal and prefrontal cortex involvement in verbal working memory employing single-pulse transcranial magnetic stimulation (TMS). In six healthy volunteers the left or right inferior parietal and prefrontal cortex was stimulated with the aid of a frameless stereotactic system. TMS was applied at 10 different time points 140-500 ms into the delay period of a two-back verbal working memory task. A choice reaction task was used as a control task. Interference with task accuracy was induced by TMS earlier in the parietal cortex than in the prefrontal cortex and earlier over the right than the left hemisphere. This suggests a propagation of information flow from posterior to anterior cortical sites converging in the left prefrontal cortex. Significant interference with reaction time was observed after 180 ms with left prefrontal cortex stimulation. These effects were not observed in the control task, underlining the task specificity of our results. We propose that the interference with right-sided prefrontal cortex stimulation leads to impaired performance due to disturbed input into the left prefrontal cortex, whereas left-sided TMS interferes directly with the final information processing. Left- and right-sided brain areas might be involved in parallel processing of semantic and object features of the stimuli, respectively.

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.

The translating brain: cerebral activation patterns during simultaneous interpreting

Brain activation was measured in professional interpreters during simultaneous interpreting (SI) vs. repetition (shadowing) of auditorily presented text by positron emission tomography (PET). SI into the native language (Finnish) elicited left frontal activation increases. SI into the non-native language (English) elicited much more extensive left-sided fronto-temporal activation increases. Our results indicate that SI activates predominantly left-hemispheric structures (particularly the left dorsolateral frontal cortex) previously related to lexical search, semantic processing and verbal working memory. Brain activation patterns were clearly modulated by direction of translation, with more extensive activation during translation into the non-native language which is often considered to a be more demanding task.

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.

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

Abstractu2002The 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.

Modulation of a brain-behavior relationship in verbal working memory by rTMS.

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.

Visuospatial working memory and changes of the point of view in 3D space

We used functional magnetic resonance imaging to explore the brain mechanisms of changing point of view (PoV) in a visuospatial memory task in 3D space. Eye movements were monitored and BOLD signal changes were measured while subjects were presented with 3D images of a virtual environment. Subjects were required to encode the position of a lamp in the environment and, after changing the PoV (angular difference varied from 0 degrees to 180 degrees in 45 degrees steps), to decide whether the lamp position had been changed too or not. Performance data and a scan-path analysis based on eye movement support the use of landmarks in the environment for coding lamp position and increasing spatial updating costs with increasing changes of PoV indicating allocentric coding strategies during all conditions (0 degrees - to 180 degrees -condition). Subtraction analysis using SPM revealed that a parieto-temporo-frontal network including left medial temporal areas was activated during this 3D visuospatial task, independent of angular difference. The activity of the left parahippocampal area and the left lingual gyrus (but not the hippocampus) correlated with increasing changes of the PoV between encoding and retrieval, emphasizing their specific role in spatial scene memory and allocentric coding. The results suggest that these areas are involved in a continuous matching process between internal representations of the environment and the external status quo. In addition, hippocampal activation correlated with performance was found indicating successful recall of spatial information. Finally, in a prefrontal area comprising, the so-called deep frontal eye field, activation was correlated with the amount of saccadic eye movements confirming its role in oculomotor processes.