Cherie L. Marvel

Consensus Paper: The Cerebellum's Role in Movement and Cognition

While the cerebellums role in motor function is well recognized, the nature of its concurrent role in cognitive function remains considerably less clear. The current consensus paper gathers diverse views on a variety of important roles played by the cerebellum across a range of cognitive and emotional functions. This paper considers the cerebellum in relation to neurocognitive development, language function, working memory, executive function, and the development of cerebellar internal control models and reflects upon some of the ways in which better understanding the cerebellums status as a “supervised learning machine” can enrich our ability to understand human function and adaptation. As all contributors agree that the cerebellum plays a role in cognition, there is also an agreement that this conclusion remains highly inferential. Many conclusions about the role of the cerebellum in cognition originate from applying known information about cerebellar contributions to the coordination and quality of movement. These inferences are based on the uniformity of the cerebellums compositional infrastructure and its apparent modular organization. There is considerable support for this view, based upon observations of patients with pathology within the cerebellum.

Consensus Paper: Language and the Cerebellum: an Ongoing Enigma

In less than three decades, the concept “cerebellar neurocognition” has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the “linguistic cerebellum” in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper.

Functional Topography of the Cerebellum in Verbal Working Memory

Speech—both overt and covert—facilitates working memory by creating and refreshing motor memory traces, allowing new information to be received and processed. Neuroimaging studies suggest a functional topography within the sub-regions of the cerebellum that subserve verbal working memory. Medial regions of the anterior cerebellum support overt speech, consistent with other forms of motor execution such as finger tapping, whereas lateral portions of the superior cerebellum support speech planning and preparation (e.g., covert speech). The inferior cerebellum is active when information is maintained across a delay, but activation appears to be independent of speech, lateralized by modality of stimulus presentation, and possibly related to phonological storage processes. Motor (dorsal) and cognitive (ventral) channels of cerebellar output nuclei can be distinguished in working memory. Clinical investigations suggest that hyper-activity of cerebellum and disrupted control of inner speech may contribute to certain psychiatric symptoms.

Attentional bias for nondrug reward is magnified in addiction.

Attentional biases for drug-related stimuli play a prominent role in addiction, predicting treatment outcomes. Attentional biases also develop for stimuli that have been paired with nondrug rewards in adults without a history of addiction, the magnitude of which is predicted by visual working-memory capacity and impulsiveness. We tested the hypothesis that addiction is associated with an increased attentional bias for nondrug (monetary) reward relative to that of healthy controls, and that this bias is related to working-memory impairments and increased impulsiveness. Seventeen patients receiving methadone-maintenance treatment for opioid dependence and 17 healthy controls participated. Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11; Patton, Stanford, & Barratt, 1995), visual working-memory capacity was measured as the ability to recognize briefly presented color stimuli, and attentional bias was measured as the magnitude of response time slowing caused by irrelevant but previously reward-associated distractors in a visual-search task. The results showed that attention was biased toward the distractors across all participants, replicating previous findings. It is important to note, this bias was significantly greater in the patients than in the controls and was negatively correlated with visual working-memory capacity. Patients were also significantly more impulsive than controls as a group. Our findings demonstrate that patients in treatment for addiction experience greater difficulty ignoring stimuli associated with nondrug reward. This nonspecific reward-related bias could mediate the distracting quality of drug-related stimuli previously observed in addiction.

An fMRI Investigation of Cerebellar Function During Verbal Working Memory in Methadone Maintenance Patients

Working memory is impaired in opioid-dependent individuals, yet the neural underpinnings of working memory in this population are largely unknown. Previous studies in healthy adults have demonstrated that working memory is supported by a network of brain regions that includes a cerebro-cerebellar circuit. The cerebellum, in particular, may be important for inner speech mechanisms that assist verbal working memory. This study used functional magnetic resonance imaging to examine brain activity associated with working memory in five opioid-dependent, methadone-maintained patients and five matched, healthy controls. An item recognition task was administered in two conditions: (1) a low working memory load “match” condition in which participants determined whether target letters presented at the beginning of the trial matched a probe item, and (2) a high working memory load “manipulation” condition in which participants counted two alphabetical letters forward of each of the targets and determined whether either of these new items matched a probe item. Response times and accuracy scores were not significantly different between the groups. FMRI analyses indicated that, in association with higher working memory load (“manipulation” condition), the patient group exhibited hyperactivity in the superior and inferior cerebellum and amygdala relative to that of controls. At a more liberal statistical threshold, patients exhibited hypoactivity in the left prefrontal and medial frontal/pre-SMA regions. These results indicate that verbal working memory in opioid-dependent individuals involves a disrupted cerebro-cerebellar circuit and shed light on the neuroanatomical basis of working memory impairments in this population.

The Neural Correlates of Implicit Sequence Learning in Schizophrenia

Twenty-seven schizophrenia spectrum patients and 25 healthy controls performed a probabilistic version of the serial reaction time task (SRT) that included sequence trials embedded within random trials. Patients showed diminished, yet measurable, sequence learning. Postexperimental analyses revealed that a group of patients performed above chance when generating short spans of the sequence. This high-generation group showed SRT learning that was similar in magnitude to that of controls. Their learning was evident from the very 1st block; however, unlike controls, learning did not develop further with continued testing. A subset of 12 patients and 11 controls performed the SRT in conjunction with positron emission tomography. High-generation performance, which corresponded to SRT learning in patients, correlated to activity in the premotor cortex and parahippocampus. These areas have been associated with stimulus-driven visuospatial processing. Taken together, these results suggest that a subset of patients who showed moderate success on the SRT used an explicit stimulus-driven strategy to process the sequential stimuli. This adaptive strategy facilitated sequence learning but may have interfered with conventional implicit learning of the overall stimulus pattern.

Reward, attention, and HIV-related risk in HIV+ individuals

Human immunodeficiency virus (HIV) is often contracted through engaging in risky reward-motivated behaviors such as needle sharing and unprotected sex. Understanding the factors that make an individual more vulnerable to succumbing to the temptation to engage in these risky behaviors is important to limiting the spread of HIV. One potential source of this vulnerability concerns the degree to which an individual is able to resist paying attention to irrelevant reward information. In the present study, we examine this possible link by characterizing individual differences in value-based attentional bias in a sample of HIV+ individuals with varying histories of risk-taking behavior. Participants learned associations between experimental stimuli and monetary reward outcome. The degree of attentional bias for these reward-associated stimuli, reflected in their ability to capture attention when presented as task-irrelevant distractors, was then assessed both immediately and six months following reward learning. Value-driven attentional capture was related to substance abuse history and non-planning impulsiveness during the time leading up to contraction of HIV as measured via self-report. These findings suggest a link between the ability to ignore reward-associated information and prior HIV-related risk-taking behavior. Additionally, particular aspects of HIV-associated neurocognitive disorders were related to attentional bias, including motor deficits commonly associated with HIV-induced damage to the basal ganglia.

Motor system contributions to verbal and non-verbal working memory.

Working memory (WM) involves the ability to maintain and manipulate information held in mind. Neuroimaging studies have shown that secondary motor areas activate during WM for verbal content (e.g., words or letters), in the absence of primary motor area activation. This activation pattern may reflect an inner speech mechanism supporting online phonological rehearsal. Here, we examined the causal relationship between motor system activity and WM processing by using transcranial magnetic stimulation (TMS) to manipulate motor system activity during WM rehearsal. We tested WM performance for verbalizable (words and pseudowords) and non-verbalizable (Chinese characters) visual information. We predicted that disruption of motor circuits would specifically affect WM processing of verbalizable information. We found that TMS targeting motor cortex slowed response times (RTs) on verbal WM trials with high (pseudoword) vs. low (real word) phonological load. However, non-verbal WM trials were also significantly slowed with motor TMS. WM performance was unaffected by sham stimulation or TMS over visual cortex (VC). Self-reported use of motor strategy predicted the degree of motor stimulation disruption on WM performance. These results provide evidence of the motor system’s contributions to verbal and non-verbal WM processing. We speculate that the motor system supports WM by creating motor traces consistent with the type of information being rehearsed during maintenance.

Cognition: Cerebellum Role

Evidence that the cerebellum is not purely devoted to motor control comes from neuroimaging studies of healthy individuals and from neuropsychological testing of patients with disorders that affect the cerebellum. Data suggest that the cerebellum contributes to cognitive processes, including executive function. Specific cerebellar contributions to cognition are not well understood. However, operations of closed cerebro-cerebellar loops likely provide the means by which the cerebellum supports a range of essential functions, from the coordination of basic motor execution to the synchronization of higher order planning and executive control.

Onset and Remission of Psychosis in Parkinson's Disease: Pharmacologic and Motoric Markers

Psychosis is among the most disabling complications of Parkinsons disease (PD). The chronicity of PD psychosis remains understudied, and the relative importance of dopaminergic therapy versus the disease process itself in engendering psychosis remains unclear. The objective of this study was to examine pharmacologic and motoric correlates of PD psychosis onset and remission in a longitudinally monitored PD cohort.