Hans J. Markowitsch

Episodic and declarative memory: Role of the hippocampus

The fact that medial temporal lobe structures, including the hippocampus, are critical for declarative memory is firmly established by now. The understanding of the role that these structures play in declarative memory, however, despite great efforts spent in the quest, has eluded investigators so far. Given the existing scenario, novel ideas that hold the promise of clarifying matters should be eagerly sought. One such idea was recently proposed by Vargha‐Khadem and her colleagues (Science 1997;277:376–380) on the basis of their study of three young people suffering from anterograde amnesia caused by early‐onset hippocampal pathology. The idea is that the hippocampus is necessary for remembering ongoing lifes experiences (episodic memory), but not necessary for the acquisition of factual knowledge (semantic memory). We discuss the reasons why this novel proposal makes good sense and why it and its ramifications should be vigorously pursued. We review and compare declarative and episodic theories of amnesia, and argue that the findings reported by Vargha‐Khadem and her colleagues fit well into an episodic theory that retains components already publicized, and adds new ones suggested by the Vargha‐Khadem et al. study. Existing components of this theory include the idea that acquisition of factual knowledge can occur independently of episodic memory, and the idea that in anterograde amnesia it is quite possible for episodic memory to be more severely impaired than semantic memory. We suggest a realignment of organization of memory such that declarative memory is defined in terms of features and properties that are common to both episodic and semantic memory. The organization of memory thus modified gives greater precision to the Vargha‐Khadem et al. neuroanatomical model in which declarative memory depends on perihippocampal cortical regions but not on the hippocampus, whereas episodic memory, which is separate from declarative memory, depends on the hippocampus. Hippocampus 1998;8:198–204.

Cerebral Representation of One's Own Past: Neural Networks Involved in Autobiographical Memory

We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using H215O positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e., subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal lobes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.

Mirror Neuron and Theory of Mind Mechanisms Involved in Face-to-Face Interactions: A Functional Magnetic Resonance Imaging Approach to Empathy

Empathy allows emotional psychological inference about other persons mental states and feelings in social contexts. We aimed at specifying the common and differential neural mechanisms of self- and other-related attribution of emotional states using event-related functional magnetic resonance imaging. Subjects viewed faces expressing emotions with direct or averted gaze and either focused on their own emotional response to each face (self-task) or evaluated the emotional state expressed by the face (other-task). The common network activated by both tasks included the left lateral orbito-frontal and medial prefrontal cortices (MPFC), bilateral inferior frontal cortices, superior temporal sulci and temporal poles, as well as the right cerebellum. In a subset of these regions, neural activity was significantly correlated with empathic abilities. The self- (relative to the other-) task differentially activated the MPFC, the posterior cingulate cortex (PCC)/precuneus, and the temporo-parietal junction bilaterally. Empathy-related processing of emotional facial expressions recruited brain areas involved in mirror neuron and theory-of-mind (ToM) mechanisms. The differential engagement of the MPFC, the PCC/precuneus, and temporo-parietal regions in the self-task indicates that these structures act as key players in the evaluation of ones own emotional state during empathic face-to-face interaction. Activation of mirror neurons in a task relying on empathic abilities without explicit task-related motor components supports the view that mirror neurons are not only involved in motor cognition but also in emotional interpersonal cognition. An interplay between ToM and mirror neuron mechanisms may hold for the maintenance of a self-other distinction during empathic interpersonal face-to-face interactions.

Neuropsychological correlates of decision-making in ambiguous and risky situations

Decision-making situations in real life differ regarding their explicitness of positive and negative consequences as well as regarding the directness of probabilities for reward and punishment. In neuropsychological research, decisions under ambiguity and decisions under risk are differentiated. To assess decisions under ambiguity the Iowa Gambling Task (IGT) is one of the most frequently used tasks. Decisions under risk can be measured by a task that offers explicit rules for gains and losses and stable winning probabilities, as the Game of Dice Task (GDT) does. In this contribution we firstly summarize studies that investigated decision-making in various groups of patients using the IGT or the GDT. We also propose a new model of decision-making in risky situations and describe differences between decisions under ambiguity and decisions under risk from a theoretical and clinical perspective.

Decision-Making Deficits of Korsakoff Patients in a New Gambling Task With Explicit Rules: Associations With Executive Functions.

Decision-making deficits reflected by risky decisions in gambling tasks have been associated with frontal lobe dysfunctions in various neurologic and psychiatric populations. The question remains whether decision-making impairments are related to executive functions. The authors developed a new gambling task, the Game of Dice Task, with explicit and stable rules for reinforcement and punishment, to investigate relations between executive functions and risk-taking behavior in an explicit decision-making situation. A sample of 35 alcoholic Korsakoff patients and 35 healthy controls was examined with the Game of Dice Task and a neuropsychological test battery. Results show that Korsakoff patients are strongly impaired in this explicit decision-making task and that these disturbances are correlated with specific executive functions.

Involvement of the amygdala in learning and memory: a critical review, with emphasis on anatomical relations

The amygdala has been attributed with a considerable number of very diverse functions. Its involvement in learning and memory, though, has found increased attention. Following a short description of the connections of the amygdala and its critical neurotransmitters, studies are reviewed here in which the amygdalas activity was manipulated or observed by different methods (lesions, electrical brain stimulation, neurochemical intra-amygdaloid injections, single-unit recordings). Some of the major conclusions resulting from this data analysis indicate an advantage in performing subtotal amygdaloid lesions over an amygdalectomy, a point of view that is especially supported by the heterogeneous anatomical connections of different amygdaloid nuclei. Thereafter, an evaluation is made of different tasks with respect to their discriminative sensitivity to amygdaloid manipulations. Some species-specific differences in performing certain tasks after amygdaloid injuries are discussed in relation to the different expansion of amygdalo-cortical connections in higher and less highly encephalized species. Finally, some general assumptions are made on the specific role of each of the amygdaloid nuclei during the mnemonic processes attributed to the amygdala. It is concluded that emotionally significant information is encoded and can be retrieved on the basis of the structures and connections of the basolateral limbic circuit.

Decision-making impairments in patients with pathological gambling

Pathological gambling (PG) is most likely associated with functional brain changes as well as neuropsychological and personality alterations. Recent research with the Iowa Gambling Task suggests decision-making impairments in PG. These deficits are usually attributed to disturbances in feedback processing and associated functional alterations of the orbitofrontal cortex. However, previous studies with other clinical populations found relations between executive (dorsolateral prefrontal) functions and decision-making using a task with explicit rules for gains and losses, the Game of Dice Task. In the present study, we assessed 25 male PG patients and 25 male healthy controls with the Game of Dice Task. PG patients showed pronounced deficits in the Game of Dice Task, and the frequency of risky decisions was correlated with executive functions and feedback processing. Therefore, risky decisions of PG patients might be influenced by both dorsolateral prefrontal and orbitofrontal cortex dysfunctions.

Thalamic mediodorsal nucleus and memory: a critical evaluation of studies in animals and man.

Following a general description of the anatomical organization of the thalamic mediodorsal nucleus (MD) of animals and man, the involvement of this nucleus in the processing of memory related information has been evaluated by reviewing stimulation, electrophysiological, and lesion studies in animals, and by reviewing research on induced lesions, degenerative changes and vascular damage of MD in humans. Neither the results from animal experiments nor those from studies on humans provide clear-cut evidence for a specific, memory related role of MD. However, the findings here presented do support the theory that MD is one of several, possible memory related relay stations. While therapeutically induced and circumscribed lesions of MD rarely result in long-lasting memory deficits, pathological processes in MD are more likely to be followed by severe memory disturbances if one or more particular structures in addition to MD are included in the lesioned regions. Consequently, it is emphasized that only the disruption of more than one site along memory related pathways will result in severe and enduring memory deficits. To account for apparent inter-species differences in the involvement of MD in memory related processes, it has been argued that MD and its principal cortical target region might basically be involved in arousal and emotional processes, but that for primates and especially for man the phylogenetically young parvocellular sector of MD and its cortical projection region, the dorsolateral prefrontal cortex, are furthermore involved in memory functions, which are modulated by emotional factors via the rest of MD and the prefrontal cortex.

Which brain regions are critically involved in the retrieval of old episodic memory

Memory is two-sided like the head of Janus: it looks into the past (retrograde memory) and the future (anterograde memory). While current opinion assumes a strong anatomical interdigitation in the processing of either kind of memory, recent single case reports and results obtained with the positron emission tomographic subtraction method indicate the likely existence of a dissociation: regions of the limbic system are primarily engaged in the encoding of autobiographical and semantic information, while cortical areas in the orbitofrontal and anterolateral temporo-polar regions are principally engaged in information retrieval. Within this retrieval system the right hemisphere may subserve episodic memory retrieval, and the left retrieval from the knowledge system (semantic memory).

Decision-making impairments in patients with Parkinson's disease

A high percentage of Parkinson’s disease (PD) patients show cognitive impairments in addition to the cardinal motor symptoms. These deficits primarily concern executive functions most probably linked to dysfunctions in prefrontal regions due to decreased dopaminergic transmission in fronto-striatal loops. To investigate possible associations between decision-making and executive functions in PD, we examined 20 non-demented PD patients and 20 healthy control subjects with a neuropsychological test battery and the Game of Dice Task. In this computerised decision-making task, the rules for gains and losses and the winning probabilities are obvious and stable. Thus, strategic components besides feedback processing might influence decision-making in this task. We found that PD patients were impaired in the Game of Dice task performance and that the frequency of disadvantageous choices correlated with both executive functions and feedback processing. We suggest that decision-making deficits of PD patients in explicit gambling situations might be associated with dysfunctions in two different fronto-striatal loops: the limbic-orbitofrontal-striatal loop, involved in feedback processing, and the dorsolateral prefrontal-striatal loop, involved in executive functions.