Many hats: intra-trial and reward-level dependent bold activity in the striatum and premotor cortex

2012 Spring.Includes bibliographical references.Lesion, drug, single-cell recording, as well as human fMRI studies, suggest dopaminergic projections from VTA/SNc (ventral tagmental area/substantia nigra pars compacta) and cortically driven striatal activity plays a key role in associating sensory events with rewarding actions both by facilitating reward processing and prediction (i.e. reinforcement learning) and biasing and later updating action selection. We, for the first time, isolated BOLD signal changes for stimulus, pre-response, response and feedback delivery at three reward levels. This design allowed us to estimate the degree of involvement of individual striatal regions across these trial components, the reward sensitivity of each component and allowed for a novel comparison of potential (and potentially competing) reinforcement learning computations. Striatal and lateral premotor cortex regions of interest (ROIs) significant activations were universally observed (excepting the ventral striatum) during stimulus presentation, pre-response, response and feedback delivery, confirming these areas importance in all aspects of visuomotor learning. The head of the caudate showed a precipitous drop in activity pre-response, while in the body of the caudate showed no significant changes in activity. The putamen peaked in activity during response. Activation in the lateral premotor cortex was strongest during stimulus presentation, but the drop off was followed by a trend of increasing activity as feedback approached. Both the head and body of the caudate as well as the putamen displayed reward-level sensitivity only during stimulus, while the ventral striatum showed reward sensitivity at both stimulus and feedback. The lack of reward sensitivity surrounding response is inconsistent with theories that the head and ventral striatum encode the value of actions. Which of the three examined reinforcement learning models correlated best with BOLD signal changes varied as a function of trial component and ROI suggesting these regions computations vary depending on task demand

Representation of Multiple, Independent Categories in the Primate Prefrontal Cortex

Neural correlates of visual categories have been previously identified in the prefrontal cortex (PFC). However, whether individual neurons can represent multiple categories is unknown. Varying degrees of generalization versus specialization of neurons in the PFC have been theorized. We recorded from lateral PFC neural activity while monkeys switched between two different and independent categorical distinctions (Cats versus Dogs, Sports Cars versus Sedans). We found that many PFC neurons reflected both categorical distinctions. In fact, these multitasking neurons had the strongest category effects. This stands in contrast to our lab's recent report that monkeys switching between competing categorical distinctions (applied to the same stimulus set) showed independent representations. We suggest that cognitive demands determine whether PFC neurons function as category “multitaskers.”National Institute of Mental Health (U.S.) (Grant 2R01MH065252-06

The neurocognition of developmental disorders of language

Developmental disorders of language include developmental language disorder, motor-speech disorders such as articulation disorder and stuttering, and dyslexia. These disorders have been explained by various accounts, which generally focus on their behavioral rather than neural characteristics, their processing rather than learning impairments, and each disorder separately rather than together, despite their commonalities and comorbidities. Here we update and review a unifying neurocognitive account, the Procedural circuit Deficit Hypothesis (PDH). The PDH posits that abnormalities of brain structures underlying procedural memory (learning and memory that relies on the basal ganglia and associated circuitry) can explain numerous brain and behavioral characteristics, across learning and processing, in multiple disorders, including both commonalities and differences. We describe procedural memory, examine its role in multiple aspects of language, and then present the PDH and relevant evidence across language-related disorders. The PDH has substantial explanatory power, and both basic research and translational implications

How may the basal ganglia contribute to auditory categorization and speech perception?

Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language-specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood

Tyvitumakkeiden harmaan aineen tilavuuden ja asymmetrian yhteys lasten proseduraalisen muistin toimintaan liittyviin kielellisiin taitoihin

Tässä tutkielmassa tutkittiin, onko tyvitumakkeiden rakenteista aivokuorukan ja häntätumakkeen harmaan aineen määrällä tai asymmetrialla yhteyttä viisivuotiaiden lasten kielellisiin taitoihin. Tutkielman taustateoriana on proseduraalisen häiriön hypoteesi (Ullman & Pierpont, 2005; Ullman ym., 2019), jonka mukaan kielen kehityksen haasteet aiheutuvat proseduraalisen oppimisen häiriintymisestä. Teorian mukaan proseduraalisen muistin häiriintymiseen vaikuttavat proseduraalisen järjestelmän taustalla olevien aivorakenteiden, mukaan lukien tyvitumakkeiden, poikkeavuudet. Aikaisemmissa tutkimuksissa lasten, joilla on kehityksellinen kielihäiriö, ja tyypillisesti kehittyvien lasten väliltä on löydetty toisistaan eriäviä tuloksia tyvitumakkeiden rakennepoikkeavuuksista. Keskenään erilaisia tuloksia saattavat selittää erot tutkimusten menetelmissä sekä tutkittavien kielellisten haasteiden eri tasot eri tutkimuksissa. Tässä tutkielmassa tarkasteltiin, ennustavatko aivokuorukan ja häntätumakkeen harmaan aineen tilavuus tai asymmetria proseduraalisen muistin toimintaan liittyviä kielellisiä taitoja koko kielellisten taitojen jatkumon sisältävässä aineistossa. Tutkittavat (n = 69) kuuluivat FinnBrain-kohorttitutkimuksen otokseen. Tutkittavien kielellisiä taitoja mitattiin Reynell III -testillä ja Fonologiatestillä. Tietoa aivokuorukan ja häntätumakkeen harmaan aineen määrästä kerättiin rakenteellisella MRI-kuvantamisella. MRI-kuvantamisesta saadun tiedon perusteella kunkin aivoalueen asymmetria määritettiin asymmetrisyysindeksin avulla. Tutkielman päälöydöksenä oli, että aivokuorukan ja häntätumakkeen harmaan aineen määrä tai asymmetria eivät olleet lasten kielellisten taitojen merkittäviä selittäjiä. Tutkielmassa havaittiin, että aivokuorukan ja häntätumakkeen harmaan aineen tilavuus tai asymmetrisyysindeksi eivät olleet lineaarisesti yhteydessä lasten lausetasoisten kielellisten taitojen kanssa. Lisäksi tulosten perusteella todettiin, että aivokuorukan ja häntätumakkeen harmaan aineen tilavuudella tai asymmetrialla ei pystytty ennustamaan lapsen fonologisia taitoja. Tulokset viittaavat siihen, että proseduraalisen häiriön hypoteesin mukaiset muutokset aivojen harmaan aineen määrässä eivät näy tyvitumakkeiden rakenteiden harmaan aineen muutoksena. Tulosta saattavat selittää tutkielman menetelmiin liittyvät valinnat, kuten aivoalueiden suuri anatominen rajaus. Toisaalta tulokset saattavat tarkoittaa, että proseduraalisen häiriön hypoteesin vastaisesti muutokset tyvitumakkeiden rakenteissa eivät ainakaan yksin riitä selittämään lasten kielen kehityksen vaikeuksia

Role Of The Dorsal Striatum In Learning and Decision Making

The striatum, the input region of the basal ganglia, has been shown to mediate many cognitive functions. The striatum itself can be functionally segregated into dorsal (DS) and ventral striatum (VS). For more than 60 years, DS has been reported to mediate stimulus-response learning, though evidence has been accruing pointing to a role in decision making. These literatures have been growing independently and an aim of this thesis was to bridge these two bodies of knowledge. We directly investigated the role of DS in stimulus-response learning versus decision making using functional magnetic resonance imaging (fMRI) in patients with Parkinson’s disease (Chapter 2) and obsessive compulsive disorder (Chapter 3). In Chapter 4, the role of DS in stimulus-response habit learning was tested in healthy individuals using fMRI. In three separate experiments (Chapters 2-4), all of the results strongly support the notion that DS mediates decision making and not learning. DS is implicated in many disorders ranging from Parkinson’s disease, obsessive compulsive disorder and addiction, and clarifying the role of DS in cognitive function is paramount for understanding substrates of disease and developing treatments

Functional role of the striatum in stimulus-response learning: Evidence from functional MRI and patients with Parkinson\u27s disease

Cognitive impairment is recognized in Parkinson’s disease (PD). Understanding striatum-mediated cognitive functions will help elucidate some of these abnormalities. Learning is often impaired by dopaminergic medication. However, dorsal striatum (DS) has been implicated in learning; an unexpected result given that dopaminergic therapy, the gold standard treatment for PD, remediates DS functioning. In two separate experiments, stimulus-response association learning and decision-making were examined in healthy individuals using functional magnetic resonance imaging (fMRI), and in PD patients using behavioural methods. In Experiment 1, healthy individuals completed a stimulus-response learning task, and brain regions associated with learning versus decision-making were investigated using fMRI. In Experiment 2, patients with PD completed a similar task on and off their dopaminergic medication. Results from both experiments suggest that DS mediates decision-making and not learning. This greater understanding of striatum-mediated cognition will ultimately prompt clinicians to devise medication strategies that consider both motor and cognitive symptoms of PD

Pharmacogenetics of Non-Motor Symptoms in Parkinson\u27s Disease

Memory deficits are recognized in Parkinson’s disease (PD). The nature of these memory deficits is unclear because few studies have both isolated memory encoding and retrieval processes while testing patients on and off their dopamine replacement medication. Previous work suggests encoding depends upon regions innervated by the ventral tegmental area, which is relatively spared in PD, while retrieval depends upon dorsal striatum, which is dopamine deficient even early in PD. We investigated the impact of a dopamine transporter (DAT1), a dopamine reuptake protein, polymorphism (a 40-base-pair variable repeat affecting expression) on encoding and retrieval in healthy, elderly controls as well as in patients on and off medication. We only found encoding deficits in PD patients who carry a DAT1 polymorphism when on, relative to off, medication, suggesting interactive effects of medication and genotype. We found improvements in memory retrieval in patients who were on, relative to off, medication, but this effect may be independent of DAT1 genotype. This work demonstrates the need for further investigation of interactive effects of medication and genetic profile in PD

The Neural Substrates of Deterministic Decision-making

When making a decision, we draw upon multiple mnemonic resources to inform our behavior and to ideally produce a good outcome. Multiple memory systems guide this process, including a medial temporal lobe (MTL) system and a striatal system. The MTL provides episodic details about specific instances of prior experience, whereas the striatum provides a prediction about possible outcomes based upon a fusion of many prior experiences. While both of these systems are assumed to support decision behavior, extricating their discrete contributions has been challenging. Using neuroimaging and computational reinforcement learning, this study investigated the extent to which the MTL and striatal systems are co-active during single-exposure learning and how these systems each support subsequent behavior. This was done in the context of a single-exposure deterministic decision-making task that separated encoding processes from subsequent decision-making processes. Human subjects learned to associate words with monetary feedback in a single decision experience. They then used that information to make better choices in a subsequent round without feedback. Activity in MTL regions predicted episodic memory accuracy and correlated with subsequent decision accuracy and response times. Additionally, the MTL supported a model-based reinforcement learning process wherein initial decision experiences were used to build a model of the environment that was then used to prospectively formulate future decision outcome predictions. Activity in striatal regions also correlated with subsequent decision accuracy and response times, but did not relate to memory accuracy. The striatum supported a model-free reinforcement learning process wherein predictions about decision outcomes were generated from a retrospective accumulation of prior decision experiences. Together, these results implicate both the MTL and striatum as essential substrates to single-exposure learning, but underscore that these systems operate in fundamentally different ways. The MTL is associated with prospective learning, wherein single instances of prior experience can be leveraged to inform subsequent choice. The striatum, in contrast, is associated with retrospective learning, wherein a history of experience is required to build reliable predictions about subsequent choices. In combination, the MTL system seems to support decision behavior until the striatal system has had enough experience to refine predictions about outcomes