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rTMS for PTSD: induced merciful oblivion or elimination of abnormal hypermnesia?

Neuroimaging studies and experimental data suggest that symptoms of posttraumatic stress disorder (PTSD) are associated with dysfunctions of neural circuits linking prefrontal cortex and the limbic system that have a role in autobiographic episodic memory. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been suggested to be beneficial to patients with PTSD, transiently alleviating re-experiencing as well as avoidance reactions and associated anxiety symptoms. In healthy humans, converging evidence suggests that rTMS of the right DLPFC interferes with episodic memory retrieval. Hence, we hypothesize that daily applications of rTMS in PTSD patients may reduce access to the set of autobiographical stored events, that, if re-experienced, may cause the overt PTSD symptoms.

Autobiographies as Topic↗

[Brain mechanisms involved in decision-making].

AIM: To review the studies on brain mechanisms in decision making within the framework of the somatic marker hypothesis, and based on experiments employing the Iowa Gambling Task. DEVELOPMENT: An overview of the somatic marker hypothesis is presented together with the review of the main results obtained from research in brain damaged patients, and normal subjects with functional neuroimaging studies, that have led to the identification of the neural structures involved in decision making in humans. CONCLUSIONS: The main region involved in decision making is the ventromedial prefrontal cortex, that integrates sensory, mnesic and emotional information relevant to the task. Other structures intervening in the various relevant processes in decision making are the amygdala (processing and encoding of the emotional signal and its association with contextual stimuli) and the cingulate cortex (process monitoring and response inhibition, especially in situations of uncertainty). The prefrontal dorsolateral cortex would also be involved through the necessary activation of the working memory in the decision making process, especially in the case of complex tasks.

Brain↗

Neural basis for the processes that underlie visually guided and internally guided force control in humans.

Despite an intricate understanding of the neural mechanisms underlying visual and motor systems, it is not completely understood in which brain regions humans transfer visual information into motor commands. Furthermore, in the absence of visual information, the retrieval process for motor memory information remains unclear. We report an investigation where visuomotor and motor memory processes were separated from only visual and only motor activation. Subjects produced precision grip force during a functional MRI (fMRI) study that included four conditions: rest, grip force with visual feedback, grip force without visual feedback, and visual feedback only. Statistical and subtractive logic analyses segregated the functional process maps. There were three important observations. First, along with the well-established parietal and premotor cortical network, the anterior prefrontal cortex, putamen, ventral thalamus, lateral cerebellum, intermediate cerebellum, and the dentate nucleus were directly involved in the visuomotor transformation process. This activation occurred despite controlling for the visual input and motor output. Second, a detailed topographic orientation of visuomotor to motor/sensory activity was mapped for the premotor cortex, parietal cortex, and the cerebellum. Third, the retrieval of motor memory information was isolated in the dorsolateral prefrontal cortex, ventral prefrontal cortex, and anterior cingulate. The motor memory process did not extend to the supplementary motor area (SMA) and the basal ganglia. These findings provide evidence in humans for a model where a distributed network extends over cortical and subcortical regions to control the visuomotor transformation process used during visually guided tasks. In contrast, a localized network in the prefrontal cortex retrieves force output from memory during internally guided actions.

Adult↗

Same or different? Neural correlates of happy and sad mood in healthy males.

Emotional experience in healthy men has been shown to rely on a brain network including subcortical as well as cortical areas in a complex interaction, which may be substantially influenced by many internal personal and external factors such as individuality, gender, stimulus material and task instructions. The divergent results may be interpreted by taking these considerations into account. Hence, many aspects remain to be clarified in characterizing the neural correlates underlying the subjective experience of emotion. One unresolved question refers to the influence of emotion quality on the cerebral substrates. Hence, 26 male healthy subjects were investigated with functional magnetic resonance imaging during standardized sad and happy mood induction as well as a cognitive control task to explore brain responses differentially involved in positive and negative emotional experience. Sad and happy mood in contrast to the control task produced similarly significant activations in the amygdala-hippocampal area extending into the parahippocampal gyrus as well as in the prefrontal and temporal cortex, the anterior cingulate, and the precuneus. Significant valence differences emerged when comparing both tasks directly. More activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC), the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the superior temporal gyrus during sadness. Happiness, on the other hand, produced stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and positive moods reveal distinct cortical activation foci within a common neural network, probably making the difference between qualitatively different emotional feelings.

Adult↗

Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory.

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self-continuity along the time axis of one's life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender-related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender-related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender-specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality.

Adult↗

Correlated discharges among putative pyramidal neurons and interneurons in the primate prefrontal cortex.

Neurophysiological recordings have revealed that the discharges of nearby cortical cells are positively correlated in time scales that range from millisecond synchronization of action potentials to much slower firing rate co-variations, evident in rates averaged over hundreds of milliseconds. The presence of correlated firing can offer insights into the patterns of connectivity between neurons; however, few models of population coding have taken account of the neuronal diversity present in cerebral cortex, notably a distinction between inhibitory and excitatory cells. We addressed this question in the monkey dorsolateral prefrontal cortex by recording neuronal activity from multiple micro-electrodes, typically spaced 0.2-0.3 mm apart. Putative excitatory and inhibitory neurons were distinguished based on their action potential waveform and baseline discharge rate. We tested each pair of simultaneously recorded neurons for presence of significant cross-correlation peaks and measured the correlation of their averaged firing rates in successive trials. When observed, cross-correlation peaks were centered at time 0, indicating synchronous firing consistent with two neurons receiving common input. Discharges in pairs of putative inhibitory interneurons were found to be significantly more strongly correlated than in pairs of putative excitatory cells. The degree of correlated firing was also higher for neurons with similar spatial receptive fields and neurons active in the same epochs of the behavioral task. These factors were important in predicting the strength of both short time scale (<5 ms) correlations and of trial-to-trial discharge rate covariations. Correlated firing was only marginally accounted for by motor and behavioral variations between trials. Our findings suggest that nearby inhibitory neurons are more tightly synchronized than excitatory ones and account for much of the correlated discharges commonly observed in undifferentiated cortical networks. In contrast, the discharge of pyramidal neurons, the sole projection cells of the cerebral cortex, appears largely independent, suggesting that correlated firing may be a property confined within local circuits and only to a lesser degree propagated to distant cortical areas and modules.

Animals↗

Intracerebral ERD/ERS in voluntary movement and in cognitive visuomotor task.

In order to study cerebral activity related to preparation and execution of movement, evoked and induced brain electrical activities were compared to each other and to fMRI results in voluntary self-paced movements. Also, the event-related desynchronization and synchronization (ERD/ERS) were studied in complex movements with various degrees of cognitive load. The Bereitschaftspotential (BP) and alpha (8-12 Hz) and beta (16-24 Hz) ERD/ERS rhythms in self-paced simple movements were analyzed in 14 epilepsy surgery candidates. In previous studies, the cortical sources of BP were consistently displayed contralateral to the movement in the primary motor cortex and somatosensory cortex, and bilateral in the supplementary motor area (SMA) and in the cingulate cortex. There were also small and inconstant BP generators in the ipsilateral sensorimotor, premotor, and dorsolateral prefrontal cortex. Alpha and beta ERD/ERS were also observed in these cortical regions. The distribution of contacts showing ERD or ERS was larger than of those showing BP. In contrast to BP, ERD, and ERS frequently occurred in the orbitofrontal, lateral and mesial temporal cortices, and inferior parietal lobule. The spatial location of brain activation for self-paced repetitive movements, i.e., writing simple dots, was studied using event-related functional MRI (fMRI) in 10 healthy right-handed subjects. We observed significant activation in regions known to participate in motor control: contralateral to the movement in the primary sensorimotor and supramarginal cortices, the SMA and the underlying cingulate, and, to a lesser extent, the ipsilateral sensorimotor region. When the fMRI was compared with the map of the brain areas electrically active with self-paced movements (intracerebral recordings; Rektor et al., 1994, 1998, 2001b, c; Rektor, 2003), there was an evident overlap of most results. Nevertheless, the electrophysiological studies were more sensitive in uncovering small active areas, i.e., in the premotor and prefrontal cortices. The BP and the event-related hemodynamic changes were displayed in regions known to participate in motor control. The cortical occurrence of oscillatory activities in the alpha-beta range was clearly more widespread. Four epilepsy surgery candidates with implanted depth brain electrodes performed two visuomotor-cognitive tasks with cued complex movements: a simple task--copying randomly presented letters from the monitor; and a more complex task--writing a letter other than that which appears on the monitor. The second task demanded an increased cognitive load, i.e., of executive functions. Alpha and beta ERD/ERS rhythms were evaluated. Similar results for both tasks were found in the majority of the frontal contacts, i.e., in the SMA, anterior cingulate, premotor, and dorsolateral prefrontal cortices. The most frequent observed activity was ERD in the beta rhythm; alpha ERS and ERD were also present. Significant differences between the two tasks appeared in several frontal areas--in the dorsolateral and ventrolateral prefrontal and orbitofrontal cortices (BA 9, 45, 11), and in the temporal neocortex (BA 21). In several contacts localized in these areas, namely in the lateral temporal cortex, there were significant changes only with the complex task--mostly beta ERD. Although the fMRI results fit well with the map of the evoked activity (BP), several discrepant localizations were displayed when the BP was compared with the distribution of the oscillatory activity (ERD-ERS). The BP and hemodynamic changes are closely related to the motor control areas; ERD/ERS represent the broader physiological aspects of motor execution and control. The BP probably reflects regional activation, while the more widespread ERD/ERS may reflect the spread of task-relevant information across relevant areas. In the writing tasks, the spatial distribution of the alpha-beta ERD/ERS in the frontal and lateral temporal cortices was partially task dependent. The ERD/ERS occurred there predominantly in the more complex of the writing tasks. Some sites were only active in the task with the increased demand on executive functions. In the temporal neocortex only, the oscillatory, but not the evoked, activity was recorded in the self-paced movement. The temporal appearance of changes of oscillatory activities in the self-paced movement task as well as in the cued movement task with an increased load of executive functions raises the interesting question of the role of this region in cognitive-movement information processing.

Adolescent↗

Operant conditioning and the orbitofrontal cortex in schizophrenic patients: unexpected evidence for intact functioning.

Neuroimaging and neuropsychological studies have consistently implicated dorsolateral prefrontal cortex as abnormal in schizophrenia. However, other areas of frontal cortex have received far less attention. In particular, few studies have examined orbital frontal regions with other than olfactory tests. In the present study we wished to assess the functional capability of orbital frontal cortex using a test developed by Bechara et al. (1994) that assesses a subject's capacity to acquire a preference through reward and punishment, using a gambling task that involved gains and losses of play money. Thirty normal subjects and 12 patients with schizophrenia (three undifferentiated, eight paranoid, one schizoaffective) comprised the sample in the present study. We found that patients with schizophrenia exhibited a pattern of findings similar to that of normals and dissimilar to that of patients with known orbital frontal damage. In our study, both normal subjects and schizophrenic patients chose most frequently from decks of cards in which there were frequent rewards and infrequent penalties, as might be expected on the basis of operant conditioning literature. We also found that performance on this task was not correlated with tests of working memory or long-term memory, suggesting that the development of a preference may occur implicitly. Our findings also argue against a general deficit in schizophrenia, as performance on the gambling task appeared relatively uncompromised.

Adolescent↗

A neural network reflecting decisions about human faces.

Anatomic structures have been linked to the mnemonic component of working memory, but the neural network underlying associated decision processes remains elusive. Here we present an event-related functional magnetic resonance imaging study that measured activity during the decision period of a delayed face recognition task. A double dissociation of activity between anterior cingulate cortex (ACC), and a network including left fusiform face area (FFA) and left dorsolateral prefrontal cortex (DLPFC), reflected whether a probe face matched the remembered face at the time of decision. Greater activity in the left FFA and left DLPFC correlated with probe faces that matched the remembered face; in contrast, activity in ACC was greater when the probe face did not match the remembered face. These results support a model where frontal regions act in concert with stimulus-specific temporal structures to make recognition decisions about visual stimuli.

Adult↗

Monitoring and the controlled processing of meaning: distinct prefrontal systems.

Distinct prefrontal regions are specialized for the controlled processing of semantic information. We have dissociated components of this system used in semantic decision-making across different perceptual conditions. Nineteen subjects were presented with auditory word sequences, on which they made semantic or syllabic decisions, while neural activity was measured using PET. Contrasting the semantic with syllabic tasks, there was activation within left rostral prefrontal cortex (RPFC) when the stimuli were presented as clear speech, reducing when the stimuli were presented in acoustically degraded form. In contrast, activation of the right dorsolateral prefrontal cortex (DLPFC) was observed with the degraded stimuli, an effect that inversely correlated with accuracy on the task. We have thus demonstrated two prefrontal systems where activity is differentially modulated by the "quality" of information held in working memory. This dissociation is likely to represent an alteration in the type of cognitive operations employed during task performance, where left RPFC is activated during extensive semantic elaboration and right DLPFC is recruited as the monitoring demands, associated with items held in working memory, increase. The function of these separate systems is integrated during the performance of verbal problem-solving tasks although they are differentially sensitive to stimulus degradation.

Adult↗

Estradiol alters transcription factor gene expression in primate prefrontal cortex.

Estrogen protects neurons from a variety of experimental insults in vitro, and is thought to protect from acute and chronic neurodegenerative processes in vivo. Estrogen also enhances higher-level cognitive functions that are centered in the dorsolateral prefrontal cortex (DLPFC) in human and non-human primates. To investigate genomic mechanisms involved in estrogenic effects on the primate brain in vivo, we compared transcription factor mRNA and protein expression in the DLPFC of ovariectomized rhesus monkeys treated with either vehicle or estradiol (E2). c-FOS, E2F1, and general transcription factor IIB (TFIIB) mRNA and protein expression were altered significantly by short-term E2 treatment, as shown by DNA array, in situ hybridization, and immunohistochemical and immunoblot evaluations. C-FOS expression was increased significantly whereas E2F1 and TFIIB levels were decreased in the DLPFC of E2-treated animals. These transcription factors were concentrated in cortical pyramids, as were estrogen receptors alpha and beta. These data indicate that estrogen may have direct as well as indirect effects on neuronal gene expression in the primate prefrontal cortex.

Animals↗

Electrophysiology of the frontal granular cortex. III. The cingulate-prefrontal relation in primate.

An investigation of the nature of laminar potentials and impulse discharges of units of dorsolateral prefrontal cortex (FC) evoked by stimulations of cingulate gyrus was made in rhesus monkey. Anterior cingulate stimulations evoked 1.0--1.5 msec latency waves, positive on pial surface and negative at FC depths of about 500--2000 mum with about the same time scale. Following the positive wave there was also a negative wave response. The amplitude and duration of the surface positive wave and negative wave of response varied according to the state of background EEG of the area. During steady EEG the positive wave was well developed and the negative wave was incipient but during EEG oscillations, the positive wave was markedly diminished and the negative wave enlarged. The alteration of responsiveness was also confirmed in depths by changes of reversed polarity potentials corresponding temporally to surface potentials. Discrete responses of FC were evoked at stimulus frequencies of up to 20 Hz. Higher frequencies resulted in depression of responsiveness. Alternate responses were depressed between 20 and 40 Hz and all responses were progressively depressed with still higher frequencies. Impulse discharges of FC units were evoked either singly or in bursts by the cingulate stimulations. Single impulse responses were commonly found. Presumably monosynaptic responses were in the latency range of 1.2-3.0 msec. They were found at depths of about 500 mum and 1000 mum. Long latency (7 msec) responses were also observed in the upper levels of cortex. The latency of the unitary response of a multi-impulse burst was in the range of 6.5-16 msec and the frequency of impulses in burst was in the order of 500-750 Hz. Such burst responses occurred on the declining phase of the depth negative wave evoked by the cingulate stimulation. The anterior cingulate effects were found to be distributed on the prefrontal cortex from arcuate sulcus to two-thirds distance rostrally. The unit responses were more commonly found in laminae between 0.4 and 1.0 mm depth than at other depths. The cingulate effects on FC were not affected by lesion of nucleus medialis dorsalis thalami or by ablation of the pre-motor cortex. The study discloses a basis by which functional states of limbic cortex can powerfully modulate the functioning of prefrontal neocortex of primate.

Animals↗

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe.

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.

Amidines↗

Motor imagery in normal subjects and in asymmetrical Parkinson's disease: a PET study.

OBJECTIVE: To investigate, using PET and H2(15)O, brain activation abnormalities of patients with PD during motor imagery. To determine whether motor imagery activation patterns depend on the hand used to complete the task. BACKGROUND: Previous work in PD has shown that bradykinesia is associated with slowness of motor imagery. METHODS: The PET study was performed in eight patients with PD with predominantly right-sided akinesia, and in eight age-matched control subjects, all right-handed. Regional cerebral blood flow was measured by PET and H2(15)O while subjects imagined a predetermined unimanual externally cued sequential movement with a joystick with either the left or the right hand, and during a rest condition. RESULTS: In normal subjects, the prefrontal cortex, supplementary motor area (SMA), superior parietal lobe, inferior frontal gyrus, and cerebellum were activated during motor imagery with either the left or the right hand. Contralateral primary motor cortex activation was noted only when the task was imagined with the right (dominant) hand, whereas activation of the dorsolateral prefrontal cortex was observed only during imagery with the left hand. In patients with PD, motor imagery with the right ("akinetic") hand was characterized by lack of activation of the contralateral primary sensorimotor cortex and the cerebellum, persistent activation of the SMA, and bilateral activation of the superior parietal cortex. Motor imagery with the left ("non-akinetic") hand was also abnormal, with lack of activation of the SMA compared with controls. CONCLUSIONS: In patients with PD with predominantly right-sided akinesia, brain activation during motor imagery is abnormal and may appear even with the less affected hand. In normal subjects, brain activation during motor imagery depends on the hand used in the imagined movement.

Adult↗

BDNF mRNA expression during postnatal development, maturation and aging of the human prefrontal cortex.

Brain derived neurotrophic factor (BDNF) is widely distributed in the central nervous system (CNS) and has survival-promoting actions on a variety of CNS neurons. We have examined changes in the level of BDNF mRNA expression in the dorsolateral prefrontal cortex (DLPFC) of the postnatal human brain using both RNAse protection assay and in situ hybridization. Expression of BDNF mRNA in the DLPFC was compared to that in the occipital cortex. BDNF mRNA levels vary between layers, with layer VI consistently higher than other layers in both the DLPFC and occipital regions. BDNF mRNA levels increase approximately one-third from infancy to adulthood, i.e. they are relatively low during infancy and adolescence, peak during young adulthood, and are maintained at a constant level throughout adulthood and aging. The significant increase in BDNF mRNA levels in the DLPFC during the young adult period coincides with the time when the frontal cortex matures both structurally and functionally. The increase in BDNF at this critical time in human development may have important implications for the etiology and treatment of the severe mental disorders that tend to present during this time.

Adolescent↗

Neural basis for generalized quantifier comprehension.

Generalized quantifiers like "all cars" are semantically well understood, yet we know little about their neural representation. Our model of quantifier processing includes a numerosity device, operations that combine number elements and working memory. Semantic theory posits two types of quantifiers: first-order quantifiers identify a number state (e.g. "at least 3") and higher-order quantifiers additionally require maintaining a number state actively in working memory for comparison with another state (e.g. "less than half"). We used BOLD fMRI to test the hypothesis that all quantifiers recruit inferior parietal cortex associated with numerosity, while only higher-order quantifiers recruit prefrontal cortex associated with executive resources like working memory. Our findings showed that first-order and higher-order quantifiers both recruit right inferior parietal cortex, suggesting that a numerosity component contributes to quantifier comprehension. Moreover, only probes of higher-order quantifiers recruited right dorsolateral prefrontal cortex, suggesting involvement of executive resources like working memory. We also observed activation of thalamus and anterior cingulate that may be associated with selective attention. Our findings are consistent with a large-scale neural network centered in frontal and parietal cortex that supports comprehension of generalized quantifiers.

Adult↗

Combined deficits of saccades and visuo-spatial orientation after cortical lesions.

Functionally, saccadic eye movements are closely linked to visuo-spatial orientation. Anatomically, the network of cortical areas controlling saccades also seems to be involved in spatial attention and orientation. Consequently, lesions should cause deficits in both categories. We investigated this in 34 patients with focal unilateral lesions of the posterior parietal cortex (PPC), the frontal eye fields (FEF), the supplementary motor area (SMA), or the dorsolateral prefrontal cortex (PFC). Saccadic eye movements were recorded using infrared reflection oculography. Visual hemineglect or other visuo-spatial disorders were investigated by a series of standardized paper-pencil tests. Further, the internal spatial coordinates (subjective visual vertical and subjective straight ahead) were assessed psychophysically. Depending on the site of the lesion, different patterns of deficits were identified: lesions of the PPC impaired reflexive exploration of visual space in terms of delayed and hypometric visually triggered saccades into the contralesional hemifield, related to the severity of visual hemineglect. Further, PPC lesions specifically affected basic functions of the perceptual analysis of space, such as the internal spatial coordinates and spatial constancy across saccades. The latter was tested by applying visual double-step stimuli, where saccade-related extraretinal information had to be taken into account for achieving spatial accuracy. Frontal lesions left these functions intact. FEF lesions, however, impaired systematic intentional exploration of space, thus causing an exploratory-motor type of visual hemineglect. Prefrontal (PFC) lesions impaired the working memory for saccade-related spatial information, and SMA lesions affected temporal properties such as the timing of saccadic sequences, but did not cause specific visuo-spatial deficits. In conclusion, patients with frontal or parietal cortical lesions often exhibit combined saccadic and visuo-spatial disorders, most of which are topically specific.

Brain Diseases↗

Brain mechanism of reward prediction under predictable and unpredictable environmental dynamics.

In learning goal-directed behaviors, an agent has to consider not only the reward given at each state but also the consequences of dynamic state transitions associated with action selection. To understand brain mechanisms for action learning under predictable and unpredictable environmental dynamics, we measured brain activities by functional magnetic resonance imaging (fMRI) during a Markov decision task with predictable and unpredictable state transitions. Whereas the striatum and orbitofrontal cortex (OFC) were significantly activated both under predictable and unpredictable state transition rules, the dorsolateral prefrontal cortex (DLPFC) was more strongly activated under predictable than under unpredictable state transition rules. We then modelled subjects' choice behaviours using a reinforcement learning model and a Bayesian estimation framework and found that the subjects took larger temporal discount factors under predictable state transition rules. Model-based analysis of fMRI data revealed different engagement of striatum in reward prediction under different state transition dynamics. The ventral striatum was involved in reward prediction under both unpredictable and predictable state transition rules, although the dorsal striatum was dominantly involved in reward prediction under predictable rules. These results suggest different learning systems in the cortico-striatum loops depending on the dynamics of the environment: the OFC-ventral striatum loop is involved in action learning based on the present state, while the DLPFC-dorsal striatum loop is involved in action learning based on predictable future states.

Brain↗