Publications

Abstract

The social significance of recognizing the person who talks to us is obvious, but the neural mechanisms that mediate talker identification are unclear. Regions along the bilateral superior temporal sulcus (STS) and the inferior frontal cortex (IFC) of the human brain are selective for voices, and they are sensitive to rapid voice changes. Although it has been proposed that voice recognition is supported by prototype-centered voice representations, the involvement of these category-selective cortical regions in the neural coding of such "mean voices" has not previously been demonstrated. Using fMRI in combination with a voice identity learning paradigm, we show that voice-selective regions are involved in the mean-based coding of voice identities. Voice typicality is encoded on a supra-individual level in the right STS along a stimulus-dependent, identity-independent (i.e., voice-acoustic) dimension, and on an intra-individual level in the right IFC along a stimulus-independent, identity-dependent (i.e., voice identity) dimension. Voice recognition therefore entails at least two anatomically separable stages, each characterized by neural mechanisms that reference the central tendencies of voice categories.

Abstract

In spoken language, pitch accent can mark certain information as focus, whereby more attentional resources are allocated to the focused information. Using functional magnetic resonance imaging, this study examined whether pitch accent, used for marking focus, recruited general attention networks during sentence comprehension. In a language task, we independently manipulated the prosody and semantic/pragmatic congruence of sentences. We found that semantic/pragmatic processing affected bilateral inferior and middle frontal gyrus. The prosody manipulation showed bilateral involvement of the superior/inferior parietal cortex, superior and middle temporal cortex, as well as inferior, middle, and posterior parts of the frontal cortex. We compared these regions with attention networks localized in an auditory spatial attention task. Both tasks activated bilateral superior/inferior parietal cortex, superior temporal cortex, and left precentral cortex. Furthermore, an interaction between prosody and congruence was observed in bilateral inferior parietal regions: for incongruent sentences, but not for congruent ones, there was a larger activation if the incongruent word carried a pitch accent, than if it did not. The common activations between the language task and the spatial attention task demonstrate that pitch accent activates a domain general attention network, which is sensitive to semantic/pragmatic aspects of language. Therefore, attention and language comprehension are highly interactive.

Abstract

Grammar acquisition is a high level cognitive function that requires the extraction of complex rules. While it has been proposed that offline time might benefit this type of rule extraction, this remains to be tested. Here, we addressed this question using an artificial grammar learning paradigm. During a short-term memory cover task, eighty-one human participants were exposed to letter sequences generated according to an unknown artificial grammar. Following a time delay of 15 min, 12 h (wake or sleep) or 24 h, participants classified novel test sequences as Grammatical or Non-Grammatical. Previous behavioral and functional neuroimaging work has shown that classification can be guided by two distinct underlying processes: (1) the holistic abstraction of the underlying grammar rules and (2) the detection of sequence chunks that appear at varying frequencies during exposure. Here, we show that classification performance improved after sleep. Moreover, this improvement was due to an enhancement of rule abstraction, while the effect of chunk frequency was unaltered by sleep. These findings suggest that sleep plays a critical role in extracting complex structure from separate but related items during integrative memory processing. Our findings stress the importance of alternating periods of learning with sleep in settings in which complex information must be acquired.

Abstract

Behavioral syntactic priming effects during sentence comprehension are typically observed only if both the syntactic structure and lexical head are repeated. In contrast, during production syntactic priming occurs with structure repetition alone, but the effect is boosted by repetition of the lexical head. We used fMRI to investigate the neuronal correlates of syntactic priming and lexical boost effects during sentence production and comprehension. The critical measure was the magnitude of fMRI adaptation to repetition of sentences in active or passive voice, with or without verb repetition. In conditions with repeated verbs, we observed adaptation to structure repetition in the left IFG and MTG, for active and passive voice. However, in the absence of repeated verbs, adaptation occurred only for passive sentences. None of the fMRI adaptation effects yielded differential effects for production versus comprehension, suggesting that sentence comprehension and production are subserved by the same neuronal infrastructure for syntactic processing.

Abstract

Repetition suppression in fMRI studies is generally thought to underlie behavioural facilitation effects (i.e., priming) and it is often used to identify the neuronal representations associated with a stimulus. However, this pays little heed to the large number of repetition enhancement effects observed under similar conditions. In this review, we identify several cognitive variables biasing repetition effects in the BOLD response towards enhancement instead of suppression. These variables are stimulus recognition, learning, attention, expectation and explicit memory. We also evaluate which models can account for these repetition effects and come to the conclusion that there is no one single model that is able to embrace all repetition enhancement effects. Accumulation, novel network formation as well as predictive coding models can all explain subsets of repetition enhancement effects.

Abstract

Participants were unknowingly exposed to complex regularities in a working memory task. The existence of implicit knowledge was subsequently inferred from a preference for stimuli with similar grammatical regularities. Several affective traits have been shown to influence
AGL performance positively, many of which are related to a tendency for automatic responding. We therefore tested whether the mindfulness trait predicted a reduction of grammatically congruent preferences, and used emotional primes to explore the influence of affect. Mindfulness was shown to correlate negatively with grammatically congruent responses. Negative primes were shown to result in faster and more negative evaluations.
We conclude that grammatically congruent preference ratings rely on habitual responses, and that our findings provide empirical evidence for the non-reactive disposition of the mindfulness trait.

Abstract

Previous studies have shown a significant association between reading skills and the performance on visuo-motor tasks. In order to clarify whether reading and writing skills modulate non-linguistic domains, we investigated the performance of two literacy groups on a visuo-motor integration task with non-linguistic stimuli. Twenty-one illiterate participants and twenty matched literate controls were included in the experiment. Subjects were instructed to use the right or the left index finger to point to and touch a randomly presented target on the right or left side of a touch screen. The results showed that the literate subjects were significantly faster in detecting and touching targets on the left compared to the right side of the screen. In contrast, the presentation side did not affect the performance of the illiterate group. These results lend support to the idea that having acquired reading and writing skills, and thus a preferred left-to-right reading direction, influences visual scanning. (JINS, 2007, 13, 359–364

Abstract

Irrelevant speech effect (ISE) is defined as a decrement in visually presented digit-list short-term memory performance due to exposure to irrelevant auditory material. Perhaps the most successful theoretical explanation of the effect is the changing state hypothesis. This hypothesis explains the effect in terms of confusion between amodal serial order cues, and represents a view based on the interference caused by the processing of similar order information of the visual and auditory materials. An alternative view suggests that the interference occurs as a consequence of the similarity between the visual and auditory contents of the stimuli. An important argument for the former view is the observation that ISE is almost exclusively observed in tasks that require memory for serial order. However, most short-term memory tasks require that both item and order information be retained in memory. An ideal task to investigate the sensitivity of maintenance of serial order to irrelevant speech would be one that calls upon order information but not item information. One task that is particularly suited to address this issue is serial recognition. In a typical serial recognition task, a list of items is presented and then probed by the same list in which the order of two adjacent items has been transposed. Due to the re-presentation of the encoding string, serial recognition requires primarily the serial order to be maintained while the content of the presented items is deemphasized. In demonstrating a highly significant ISE of changing versus steady-state auditory items in a serial recognition task, the present finding lends support for and extends previous empirical findings suggesting that irrelevant speech has the potential to interfere with the coding of the order of the items to be memorized.

Abstract

Common activations in prefrontal cortex (PFC) during episodic and semantic long-term memory (LTM) tasks have been hypothesized to reflect functional overlap in terms of working memory (WM) and cognitive control. To evaluate a WM account of LTM-general activations, the present study took into consideration that cognitive task performance depends on the dynamic operation of multiple component processes, some of which are stimulus-synchronous and transient in nature; and some that are engaged throughout a task in a sustained fashion. PFC and WM may be implicated in both of these temporally independent components. To elucidate these possibilities we employed mixed blocked/event-related functional magnetic resonance imaging (fMRI) procedures to assess the extent to which sustained or transient activation patterns overlapped across tasks indexing episodic and semantic LTM, attention (ATT), and WM. Within PFC, ventrolateral and medial areas exhibited sustained activity across all tasks, whereas more anterior regions including right frontopolar cortex were commonly engaged in sustained processing during the three memory tasks. These findings do not support a WM account of sustained frontal responses during LTM tasks, but instead suggest that the pattern that was common to all tasks reflects general attentional set/vigilance, and that the shared WM-LTM pattern mediates control processes related to upholding task set. Transient responses during the three memory tasks were assessed relative to ATT to isolate item-specific mnemonic processes and were found to be largely distinct from sustained effects. Task-specific effects were observed for each memory task. In addition, a common item response for all memory tasks involved left dorsolateral PFC (DLPFC). The latter response might be seen as reflecting WM processes during LTM retrieval. Thus, our findings suggest that a WM account of shared PFC recruitment in LTM tasks holds for common transient item-related responses rather than sustained state-related responses that are better seen as reflecting more general attentional/control processes.

Abstract

In an event-related fMRI study, we examined the cortical networks involved in establishing reference during language comprehension. We compared BOLD responses to sentences containing referentially ambiguous pronouns (e.g., “Ronald told Frank that he…”), referentially failing pronouns (e.g., “Rose told Emily that he…”) or coherent pronouns. Referential ambiguity selectively recruited medial prefrontal regions, suggesting that readers engaged in problem-solving to select a unique referent from the discourse model. Referential failure elicited activation increases in brain regions associated with morpho-syntactic processing, and, for those readers who took failing pronouns to refer to unmentioned entities, additional regions associated with elaborative inferencing were observed. The networks activated by these two referential problems did not overlap with the network activated by a standard semantic anomaly. Instead, we observed a double dissociation, in that the systems activated by semantic anomaly are deactivated by referential ambiguity, and vice versa. This inverse coupling may reflect the dynamic recruitment of semantic and episodic processing to resolve semantically or referentially problematic situations. More generally, our findings suggest that neurocognitive accounts of language comprehension need to address not just how we parse a sentence and combine individual word meanings, but also how we determine who's who and what's what during language comprehension.

Abstract

The current understanding of hemispheric interaction is limited. Functional hemispheric specialization is likely to depend on both genetic and environmental factors. In the present study we investigated the importance of one factor, literacy, for the functional lateralization in the inferior parietal cortex in two independent samples of literate and illiterate subjects. The results show that the illiterate group are consistently more right-lateralized than their literate controls. In contrast, the two groups showed a similar degree of left-right differences in early speech-related regions of the superior temporal cortex. These results provide evidence suggesting that a cultural factor, literacy, influences the functional hemispheric balance in reading and verbal working memory-related regions. In a third sample, we investigated grey and white matter with voxel-based morphometry. The results showed differences between literacy groups in white matter intensities related to the mid-body region of the corpus callosum and the inferior parietal and parietotemporal regions (literate > illiterate). There were no corresponding differences in the grey matter. This suggests that the influence of literacy on brain structure related to reading and verbal working memory is affecting large-scale brain connectivity more than grey matter per se.

Abstract

Using event-related functional magnetic resonance imaging, we identified brain regions involved in storing associations of events discontinuous in time into long-term memory. Participants were scanned while memorizing item-triplets including simultaneous and discontinuous associations. Subsequent memory tests showed that participants remembered both types of associations equally well. First, by constructing the contrast between the subsequent memory effects for discontinuous associations and simultaneous associations, we identified the left posterior parahippocampal region, dorsolateral prefrontal cortex, the basal ganglia, posterior midline structures, and the middle temporal gyrus as being specifically involved in transforming discontinuous associations into episodic memory. Second, we replicated that the prefrontal cortex and the medial temporal lobe (MTL) especially the hippocampus are involved in associative memory formation in general. Our findings provide evidence for distinct neural operation(s) that supports the binding and storing discontinuous associations in memory. We suggest that top-down signals from the prefrontal cortex and MTL may trigger reactivation of internal representation in posterior midline structures of the first event, thus allowing it to be associated with the second event. The dorsolateral prefrontal cortex together with basal ganglia may support this encoding operation by executive and binding processes within working memory, and the posterior parahippocampal region may play a role in binding and memory formation.

Abstract

Previous research suggests that learning an alphabetic written language influences aspects of the auditory-verbal language system. In this study, we examined whether literacy influences the notion of words as phonological units independent of lexical semantics in literate and illiterate subjects. Subjects had to decide which item in a word- or pseudoword pair was phonologically longest. By manipulating the relationship between referent size and phonological length in three word conditions (congruent, neutral, and incongruent) we could examine to what extent subjects focused on form rather than meaning of the stimulus material. Moreover, the pseudoword condition allowed us to examine global phonological awareness independent of lexical semantics. The results showed that literate performed significantly better than illiterate subjects in the neutral and incongruent word conditions as well as in the pseudoword condition. The illiterate group performed least well in the incongruent condition and significantly better in the pseudoword condition compared to the neutral and incongruent word conditions and suggest that performance on phonological word length comparisons is dependent on literacy. In addition, the results show that the illiterate participants are able to perceive and process phonological length, albeit less well than the literate subjects, when no semantic interference is present. In conclusion, the present results confirm and extend the finding that illiterate subjects are biased towards semantic-conceptual-pragmatic types of cognitive processing.

Abstract

Spaced learning with time to consolidate leads to more stabile memory traces. However, little is known about the neural correlates of trace stabilization, especially in humans. The present fMRI study contrasted retrieval activity of two well-learned sets of face-location associations, one learned in a massed style and tested on the day of learning (i.e., labile condition) and another learned in a spaced scheme over the course of one week (i.e., stabilized condition). Both sets of associations were retrieved equally well, but the retrieval of stabilized association was faster and accompanied by large-scale changes in the network supporting retrieval. Cued recall of stabilized as compared with labile associations was accompanied by increased activity in the precuneus, the ventromedial prefrontal cortex, the bilateral temporal pole, and left temporo–parietal junction. Conversely, memory representational areas such as the fusiform gyrus for faces and the posterior parietal cortex for locations did not change their activity with stabilization. The changes in activation in the precuneus, which also showed increased connectivity with the fusiform area, are likely to be related to the spatial nature of our task. The activation increase in the ventromedial prefrontal cortex, on the other hand, might reflect a general function in stabilized memory retrieval. This area might succeed the hippocampus in linking distributed neocortical representations.

Abstract

The medial temporal lobe (MTL) is crucial for declarative memory formation, but the function of its subcomponents in associative memory formation remains controversial. Most functional imaging studies on this topic are based on a stepwise approach comparing a condition with and one without associative encoding. Extending this approach we applied additionally a parametric analysis by varying the amount of associative memory formation. We found a hippocampal subsequent memory effect of almost similar magnitude regardless of the amount of associations formed. By contrast, subsequent memory effects in rhinal and parahippocampal cortices were parametrically and positively modulated by the amount of associations formed. Our results indicate that the parahippocampal region supports associative memory formation as tested here and the hippocampus adds a general mnemonic operation. This pattern of results might suggest a new interpretation. Instead of having either a fixed division of labor between the hippocampus (associative memory formation) and the rhinal cortex (non-associative memory formation) or a functionally unitary MTL system, in which all substructures are contributing to memory formation in a similar way, we propose that the location where associations are formed within the MTL depends on the kind of associations bound: If visual single-dimension associations, as used here, can already be integrated within the parahippocampal region, the hippocampus might add a general purpose mnemonic operation only. In contrast, if associations have to be formed across widely distributed neocortical representations, the hippocampus may provide a binding operation in order to establish a coherent memory.

Abstract

Progesterone, or rather its neuroactive metabolite allopregnanolone, modulates amygdala activity and thereby influences anxiety. Cognition and, in particular, memory are also altered by allopregnanolone. In the present study, we investigated whether allopregnanolone modulates memory for biologically salient stimuli by influencing amygdala activity, which in turn may affect neural processes in other brain regions. A single progesterone dose was administered orally to healthy young women in a double-blind, placebo-controlled, crossover design, and participants were asked to memorize and recognize faces while undergoing functional magnetic resonance imaging. Progesterone decreased recognition accuracy without affecting reaction times. The imaging results show that the amygdala, hippocampus, and fusiform gyrus supported memory formation. Importantly, progesterone decreased responses to faces in the amygdala and fusiform gyrus duringmemoryencoding, whereas it increased hippocampal responses. The progesterone-induced decrease in neural activity in the amygdala and fusiform gyrus predicted the decrease in memory performance across subjects. However, progesterone did not modulate the differential activation between subsequently remembered and subsequently forgotten faces in these areas. A similar pattern of results was observed in the fusiform gyrus and prefrontal cortex during memory retrieval. These results suggest that allopregnanolone impairs memory by reducing the recruitment of those brain regions that support memory formation and retrieval. Given the important role of the amygdala in the modulation of memory, these results suggest that allopregnanolone alters memory by influencing amygdala activity, which in turn may affect memory processes in other brain regions

Abstract

Rapid response to danger holds an evolutionary advantage. In this positron emission tomography study, phobics were exposed to masked visual stimuli with timings that either allowed awareness or not of either phobic, fear-relevant (e.g., spiders to snake phobics), or neutral images. When the timing did not permit awareness, the amygdala responded to both phobic and fear-relevant stimuli. With time for more elaborate processing, phobic stimuli resulted in an addition of an affective processing network to the amygdala activity, whereas no activity was found in response to fear-relevant stimuli. Also, right prefrontal areas appeared deactivated, comparing aware phobic and fear-relevant conditions. Thus, a shift from top-down control to an affectively driven system optimized for speed was observed in phobic relative to fear-relevant aware processing.

Abstract

Irrelevant speech impairs the immediate serial recall of visually presented material. Previously, we have shown that the irrelevant speech effect (ISE) was associated with a relative decrease of regional blood flow in cortical regions subserving the verbal working memory, in particular the superior temporal cortex. In this extension of the previous study, the working memory load was increased and an increased activity as a response to irrelevant speech was noted in the dorsolateral prefrontal cortex. We suggest that the two studies together provide some basic insights as to the nature of the irrelevant speech effect. Firstly, no area in the brain can be ascribed as the single locus of the irrelevant speech effect. Instead, the functional neuroanatomical substrate to the effect can be characterized in terms of changes in networks of functionally interrelated areas. Secondly, the areas that are sensitive to the irrelevant speech effect are also generically activated by the verbal working memory task itself. Finally, the impact of irrelevant speech and related brain activity depends on working memory load as indicated by the differences between the present and the previous study. From a brain perspective, the irrelevant speech effect may represent a complex phenomenon that is a composite of several underlying mechanisms, which depending on the working memory load, include top-down inhibition as well as recruitment of compensatory support and control processes. We suggest that, in the low-load condition, a selection process by an inhibitory top-down modulation is sufficient, whereas in the high-load condition, at or above working memory span, auxiliary adaptive cognitive resources are recruited as compensation

Abstract

Semantic verbal fluency tasks are commonly used in neuropsychological assessment. Investigations of the influence of level of literacy have not yielded consistent results in the literature. This prompted us to investigate the ecological relevance of task specifics, in particular, the choice of semantic criteria used. Two groups of literate and illiterate subjects were compared on two verbal fluency tasks using different semantic criteria. The performance on a food criterion (supermarket fluency task), considered more ecologically relevant for the two literacy groups, and an animal criterion (animal fluency task) were compared. The data were analysed using both quantitative and qualitative measures. The quantitative analysis indicated that the two literacy groups performed equally well on the supermarket fluency task. In contrast, results differed significantly during the animal fluency task. The qualitative analyses indicated differences between groups related to the strategies used, especially with respect to the animal fluency task. The overall results suggest that there is not a substantial difference between literate and illiterate subjects related to the fundamental workings of semantic memory. However, there is indication that the content of semantic memory reflects differences in shared cultural background - in other words, formal education –, as indicated by the significant interaction between level of literacy and semantic criterion.

Abstract

Although the sentences that we hear or read have meaning, this does not necessarily mean that they are also true. Relatively little is known about the critical brain structures for, and the relative time course of, establishing the meaning and truth of linguistic expressions. We present electroencephalogram data that show the rapid parallel integration of both semantic and world
knowledge during the interpretation of a sentence. Data from functional magnetic resonance imaging revealed that the left inferior prefrontal cortex is involved in the integration of both meaning and world knowledge. Finally, oscillatory brain responses indicate that the brain keeps a record of what makes a sentence hard to interpret.

Abstract

Spatial memory deficits are core features of aging-related changes in cognitive abilities. The neural correlates of these deficits are largely unknown. In the present study, we investigated the neural underpinnings of age-related differences in spatial memory by functional MRI using a navigational memory task with route encoding and route recognition conditions. We investigated 20 healthy young (18 - 29 years old) and 20 healthy old adults (53 - 78 years old) in a random effects analysis. Old subjects showed slightly poorer performance than young subjects. Compared to the control condition, route encoding and route recognition showed activation of the dorsal and ventral visual processing streams and the frontal eye fields in both groups of subjects. Compared to old adults, young subjects showed during route encoding stronger activations in the dorsal and the ventral visual processing stream (supramarginal gyrus and posterior fusiform/parahippocampal areas). In addition, young subjects showed weaker anterior parahippocampal activity during route recognition compared to the old group. In contrast, old compared to young subjects showed less suppressed activity in the left perisylvian region and the anterior cingulate cortex during route encoding. Our findings suggest that agerelated navigational memory deficits might be caused by less effective route encoding based on reduced posterior fusiform/parahippocampal and parietal functionality combined with diminished inhibition of perisylvian and anterior cingulate cortices correlated with less effective suppression of task-irrelevant information. In contrast, age differences in neural correlates of route recognition seem to be rather subtle. Old subjects might show a diminished familiarity signal during route recognition in the anterior parahippocampal region.

Abstract

In the present study, using event-related functional magnetic resonance imaging, we investigated a group of participants on a grammaticality classification task after they had been exposed to well-formed consonant strings generated from an artificial regular grammar.We used an implicit acquisition paradigm in which the participants were exposed to positive examples. The objective of this studywas to investigate whether brain regions related to language processing overlap with the brain regions activated by the grammaticality classification task used in the present study. Recent meta-analyses of functional neuroimaging studies indicate that syntactic processing is related to the left inferior frontal gyrus (Brodmann's areas 44 and 45) or Broca's region. In the present study, we observed that artificial grammaticality violations activated Broca's region in all participants. This observation lends some support to the suggestions that artificial grammar learning represents a model for investigating aspects of language learning in infants.

Abstract

The autonomic responses to acute pain exposure usually habituate rapidly while the subjective ratings of pain remain high for more extended periods of time. Thus, systems involved in the autonomic response to painful stimulation, for example the hypothalamus and the brainstem, would be expected to attenuate the response to pain during prolonged stimulation. This suggestion is in line with the hypothesis that the brainstem is specifically involved in the initial response to pain. To probe this hypothesis, we performed a positron emission tomography (PET) study where we scanned subjects during the first and second minute of a prolonged tonic painful cold stimulation (cold pressor test) and nonpainful cold stimulation. Galvanic skin response (GSR) was recorded during the PET scanning as an index of autonomic sympathetic response. In the main effect of pain, we observed increased activity in the thalamus bilaterally, in the contralateral insula and in the contralateral anterior cingulate cortex but no significant increases in activity in the primary or secondary somatosensory cortex. The autonomic response (GSR) decreased with stimulus duration. Concomitant with the autonomic response, increased activity was observed in brainstem and hypothalamus areas during the initial vs. the late stimulation. This effect was significantly stronger for the painful than for the cold stimulation. Activity in the brainstem showed pain-specific covariation with areas involved in pain processing, indicating an interaction between the brainstem and cortical pain networks. The findings indicate that areas in the brainstem are involved in the initial response to noxious stimulation, which is also characterized by an increased sympathetic response.

Abstract

The amygdala has been implicated in fundamental functions for the survival of the organism, such as fear and pain. In accord with this, several studies have shown increased amygdala activity during fear conditioning and the processing of fear-relevant material in human subjects. In contrast, functional neuroimaging studies of pain have shown a decreased amygdala activity. It has previously been proposed that the observed deactivations of the amygdala in these studies indicate a cognitive strategy to adapt to a distressful but in the experimental setting unavoidable painful event. In this positron emission tomography study, we show that a simple contextual manipulation, immediately preceding a painful stimulation, that increases the anticipated duration of the painful event leads to a decrease in amygdala activity and modulates the autonomic response during the noxious stimulation. On a behavioral level, 7 of the 10 subjects reported that they used coping strategies more intensely in this context. We suggest that the altered activity in the amygdala may be part of a mechanism to attenuate pain-related stress responses in a context that is perceived as being more aversive. The study also showed an increased activity in the rostral part of anterior cingulate cortex in the same context in which the amygdala activity decreased, further supporting the idea that this part of the cingulate cortex is involved in the modulation of emotional and pain networks

Abstract

Navigation through familiar environments can rely upon distinct neural representations that are related to different memory systems with either the hippo-campus or the caudate nucleus at their core. However,it is a fundamental question whether and how these systems interact during route recognition. To address this issue, we combined a functional neuroimaging approach with a naturally occurring, well-controlled humanmodel of caudate nucleus dysfunction (i.e., pre-clinical and early-stage Huntington’s disease). Our results reveal a noncompetitive interaction so that the hippocampus compensates for gradual caudate nucleus dysfunction with a gradual activity increase,maintaining normal behavior. Furthermore, we revealed an interaction between medial temporal and caudate activity in healthy subjects, which was adaptively modified in Huntington patients to allow compensatory hippocampal processing. Thus, the two memory systems contribute in a noncompetitive, co operative manner to route recognition, which enables Polthe hippocampus to compensate seamlessly for the functional degradation of the caudate nucleus