Basal Ganglia-thalamocortical Research Articles

Differential patterns of functional connectivity in tremor dominant Parkinson's disease and essential tremor plus.

Tremor dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.

Slow-wave sleep dysfunction in mild parkinsonism is associated with excessive beta and reduced delta oscillations in motor cortex.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5-3 Hz) power was reduced (p = 0.038) whereas beta (8-35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r = 0.43, p = 0.037) and negatively correlated with beta power (r = -0.65, p < 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD.

Microstructural white matter changes underlying speech deficits in Parkinson’s disease

Speech impairments are one of the common symptoms of individuals with Parkinson’s disease (PD). However, little is known about the underlying neuroanatomical structural deficits specifically in the basal ganglia-thalamocortical (BGTC) loop in the speech deficits of PD. Here we investigated white matter differences in PD using probabilistic tractography. Diffusion tensor imaging data were downloaded from the Parkinson’s Progression Markers Initiative database. We included three groups of participants: 20 PD individuals with speech deficits, 20 PD individuals without speech deficits, and 20 age- and gender-matched control participants. Overall, PD individuals with speech deficits had higher mean diffusivity in the BGTC pathway in the left hemisphere compared with PD individuals without speech deficits. The present study exhibits that there may be a distinct pathophysiological profile of white matter for speech deficits in PD.

Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson's Disease patients.

Evidence suggests that spontaneous beta band (11-35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson's disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined. We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery. Our analyses show that low-frequency (2-4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization. Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses.

Brain developmental trajectories associated with childhood stuttering persistence and recovery

Stuttering is a neurodevelopmental disorder affecting 5–8 % of preschool-age children, continuing into adulthood in 1 % of the population. The neural mechanisms underlying persistence and recovery from stuttering remain unclear and little information exists on neurodevelopmental anomalies in children who stutter (CWS) during preschool age, when stuttering symptoms typically first emerge. Here we present findings from the largest longitudinal study of childhood stuttering to date, comparing children with persistent stuttering (pCWS) and those who later recovered from stuttering (rCWS) with age-matched fluent peers, to examine the developmental trajectories of both gray matter volume (GMV) and white matter volume (WMV) using voxel-based morphometry. A total of 470 MRI scans were analyzed from 95 CWS (72 pCWS and 23 rCWS) and 95 fluent peers between 3 and 12 years of age. We examined overall group and group by age interactions in GMV and WMV in preschool age (3–5 years old) and school age (6–12 years old) CWS and controls, controlling for sex, IQ, intracranial volume, and socioeconomic status. The results provide broad support for a possible basal ganglia-thalamocortical (BGTC) network deficit starting in the earliest phases of the disorder and point to normalization or compensation of earlier occurring structural changes associated with stuttering recovery.

Brain activity during the preparation and production of spontaneous speech in children with persistent stuttering

Speech production forms the basis for human verbal communication. Though fluent speech production is effortless and automatic for most people, it is disrupted in speakers who stutter, who experience difficulties especially during spontaneous speech and at utterance onsets. Brain areas comprising the basal ganglia thalamocortical (BGTC) motor loop have been a focus of interest in the context of stuttering, given this circuit’s critical role in initiating and sequencing connected speech. Despite the importance of better understanding the role of the BGTC motor loop in supporting overt, spontaneous speech production, capturing brain activity during speech has been challenging to date, due to fMRI artifacts associated with severe head motions during speech production. Here, using an advanced technique that removes speech-related artifacts from fMRI signals, we examined brain activity occurring immediately before, and during, overt spontaneous speech production in 22 children with persistent stuttering (CWS) and 18 children who do not stutter (controls) in the 5-to-12-year age range. Brain activity during speech production was compared in two conditions: spontaneous speech (i.e., requiring language formulation) and automatic speech (i.e., overlearned word sequences). Compared to controls, CWS exhibited significantly reduced left premotor activation during spontaneous speech production but not during automatic speech. Moreover, CWS showed an age-related reduction in left putamen and thalamus activation during speech preparation. These results provide further evidence that stuttering is associated with functional deficits in the BGTC motor loop, which are exacerbated during spontaneous speech production.

The impact of pulse timing on cortical and subthalamic nucleus deep brain stimulation evoked potentials.

The impact of pulse timing is an important factor in our understanding of how to effectively modulate the basal ganglia thalamocortical (BGTC) circuit. Single pulse low-frequency DBS-evoked potentials generated through electrical stimulation of the subthalamic nucleus (STN) provide insight into circuit activation, but how the long-latency components change as a function of pulse timing is not well-understood. We investigated how timing between stimulation pulses delivered in the STN region influence the neural activity in the STN and cortex. DBS leads implanted in the STN of five patients with Parkinson's disease were temporarily externalized, allowing for the delivery of paired pulses with inter-pulse intervals (IPIs) ranging from 0.2 to 10 ms. Neural activation was measured through local field potential (LFP) recordings from the DBS lead and scalp EEG. DBS-evoked potentials were computed using contacts positioned in dorsolateral STN as determined through co-registered post-operative imaging. We quantified the degree to which distinct IPIs influenced the amplitude of evoked responses across frequencies and time using the wavelet transform and power spectral density curves. The beta frequency content of the DBS evoked responses in the STN and scalp EEG increased as a function of pulse-interval timing. Pulse intervals <1.0 ms apart were associated with minimal to no change in the evoked response. IPIs from 1.5 to 3.0 ms yielded a significant increase in the evoked response, while those >4 ms produced modest, but non-significant growth. Beta frequency activity in the scalp EEG and STN LFP response was maximal when IPIs were between 1.5 and 4.0 ms. These results demonstrate that long-latency components of DBS-evoked responses are pre-dominantly in the beta frequency range and that pulse interval timing impacts the level of BGTC circuit activation.

Regulating absence seizures by tri-phase delay stimulation applied to globus pallidus internal.

In this paper, a reduced globus pallidus internal (GPI)-corticothalamic (GCT) model is developed, and a tri-phase delay stimulation (TPDS) with sequentially applying three pulses on the GPI representing the inputs from the striatal D1 neurons, subthalamic nucleus (STN), and globus pallidus external (GPE), respectively, is proposed. The GPI is evidenced to control absence seizures characterized by 2 Hz-4 Hz spike and wave discharge (SWD). Hence, based on the basal ganglia-thalamocortical (BGCT) model, we firstly explore the triple effects of Dl-GPI, GPE-GPI, and STN-GPI pathways on seizure patterns. Then, using the GCT model, we apply the TPDS on the GPI to potentially investigate the alternative and improved approach if these pathways to the GPI are blocked. The results show that the striatum D1, GPE, and STN can indeed jointly and significantly affect seizure patterns. In particular, the TPDS can effectively reproduce the seizure pattern if the D1-GPI, GPE-GPI, and STN-GPI pathways are cut off. In addition, the seizure abatement can be obtained by well tuning the TPDS stimulation parameters. This implies that the TPDS can play the surrogate role similar to the modulation of basal ganglia, which hopefully can be helpful for the development of the brain-computer interface in the clinical application of epilepsy.

Movement-related changes in pallidocortical synchrony differentiate action execution and observation in humans

ObjectiveSuppression of local and network alpha and beta oscillations in the human basal ganglia-thalamocortical (BGTC) circuit is a prominent feature of movement, including suppression of local alpha/beta power, cross-region beta phase coupling, and cortical and subcortical phase-amplitude coupling (PAC). We hypothesized that network-level coupling is more directly related to movement execution than local power changes, given the role of pathological network hypersynchrony in movement disorders such as Parkinson disease (PD). Understanding the specificity of these movement-related signals is important for designing novel therapeutics. MethodsWe recorded globus pallidus internus (GPi) and motor cortical local field potentials during movement execution, passive movement observation and rest in 12 patients with PD undergoing deep brain stimulator implantation. ResultsLocal alpha/beta power is suppressed in the globus pallidus and motor cortex during both action execution and action observation, although less so during action observation. In contrast, pallidocortical phase synchrony and GPi and motor cortical alpha/beta-gamma PAC are suppressed only during action execution. ConclusionsThe functional dissociation across tasks in pallidocortical network activity suggests a particularly important role of network coupling in motor execution. SignificanceNetwork level recordings provide important specificity in differentiating motor behavior and may provide significant value for future closed loop therapies.

White matter microstructural differences underlying beta oscillations during speech in adults who stutter

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen.

Parkinsonism Alters Beta Burst Dynamics across the Basal Ganglia-Motor Cortical Network.

Elevated synchronized oscillatory activity in the beta band has been hypothesized to be a pathophysiological marker of Parkinson's disease (PD). Recent studies have suggested that parkinsonism is closely associated with increased amplitude and duration of beta burst activity in the subthalamic nucleus (STN). How beta burst dynamics are altered from the normal to parkinsonian state across the basal ganglia-thalamocortical (BGTC) motor network, however, remains unclear. In this study, we simultaneously recorded local field potential activity from the STN, internal segment of the globus pallidus (GPi), and primary motor cortex (M1) in three female rhesus macaques, and characterized how beta burst activity changed as the animals transitioned from normal to progressively more severe parkinsonian states. Parkinsonism was associated with an increased incidence of beta bursts with longer duration and higher amplitude in the low beta band (8-20 Hz) in both the STN and GPi, but not in M1. We observed greater concurrence of beta burst activity, however, across all recording sites (M1, STN, and GPi) in PD. The simultaneous presence of low beta burst activity across multiple nodes of the BGTC network that increased with severity of PD motor signs provides compelling evidence in support of the hypothesis that low beta synchronized oscillations play a significant role in the underlying pathophysiology of PD. Given its immersion throughout the motor circuit, we hypothesize that this elevated beta-band activity interferes with spatial-temporal processing of information flow in the BGTC network that contributes to the impairment of motor function in PD.SIGNIFICANCE STATEMENT This study fills a knowledge gap regarding the change in temporal dynamics and coupling of beta burst activity across the basal ganglia-thalamocortical (BGTC) network during the evolution from normal to progressively more severe parkinsonian states. We observed that changes in beta oscillatory activity occur throughout BGTC and that increasing severity of parkinsonism was associated with a higher incidence of longer duration, higher amplitude low beta bursts in the basal ganglia, and increased concurrence of beta bursts across the subthalamic nucleus, globus pallidus, and motor cortex. These data provide new insights into the potential role of changes in the temporal dynamics of low beta activity within the BGTC network in the pathogenesis of Parkinson's disease.

Functional connectivity of the tremor network in essential tremor plus and tremor dominant Parkinson's disease

Objective: The basal ganglia thalamo cortical (BGTC) and cerebello thalamo cortical (CTC) networks have been implicated in tremor genesis, however, the patterns of involvement of these networks across different tremor disorders has not been assessed. This study aims to compare the functional connectivity of the tremor network in essential tremor plus (ETP) and tremor dominant Parkinson's disease (TDPD).

Altered Pallidocortical Low-Beta Oscillations During Self-Initiated Movements in Parkinson Disease.

BackgroundParkinson disease (PD) patients have difficulty with self-initiated (SI) movements, presumably related to basal ganglia thalamocortical (BGTC) circuit dysfunction, while showing less impairment with externally cued (EC) movements.ObjectivesWe investigate the role of BGTC in movement initiation and the neural underpinning of impaired SI compared to EC movements in PD using multifocal intracranial recordings and correlating signals with symptom severity.MethodsWe compared time-resolved neural activities within and between globus pallidus internus (GPi) and motor cortex during between SI and EC movements recorded invasively in 13 PD patients undergoing deep brain stimulation implantation. We compared cortical (but not subcortical) dynamics with those recorded in 10 essential tremor (ET) patients, who do not have impairments in movement initiation.ResultsSI movements in PD are associated with greater low-beta (13–20 Hz) power suppression during pre-movement period in GPi and motor cortex compared to EC movements in PD and compared to SI movements in ET (motor cortex only). SI movements in PD are uniquely associated with significant low-beta pallidocortical coherence suppression during movement execution that correlates with bradykinesia severity. In ET, motor cortex neural dynamics during EC movements do not significantly differ from that observed in PD and do not significantly differ between SI and EC movements.ConclusionThese findings implicate low beta BGTC oscillations in impaired SI movements in PD. These results provide a physiological basis for the strategy of using EC movements in PD, circumventing diseased neural circuits associated with SI movements and instead engaging circuits that function similarly to those without PD.

Characterization of pallidocortical motor network in Parkinson’s disease through complex network analysis

Objective. Deep brain stimulation (DBS) has been demonstrated by numerous clinical trials to be an advanced therapy for selected patients with Parkinson’s disease (PD), while its maximal therapeutic effect is capped by the inadequate understanding of the precise neuronal mechanisms underlying PD. Recordings from multichannel electrodes placed in subcortical and cortical regions of the basal ganglia-thalamocortical (BGTC) motor network during DBS surgical procedures can provide rich physiologic information from accessible network nodes. However, most investigations focus on presumed spatio-spectral points of interest, neither fully utilizing the richness of spatial, spectral and temporal aspects of the multivariate signals nor making discoveries in the context of all possible candidates. In addition, aggregated network-level information has been missed out. Approach. We use complex network analysis to characterize functional network characteristics of the pallidocortical subcircuit of the BGTC motor network in PD at rest and with movement. The network matrix was constructed using distinct frequency bands at each anatomic recording site as virtual nodes and spectral connectivity (through phase–amplitude coupling and coherence) as network edges. Main results. We confirm the critical roles of beta bands and provide additional evidence on their differential functional roles in the pallidocortical motor network. Moreover, significant changes (p < 0.05) in network functional segregation and integration between rest and movement conditions are revealed for the first time. More importantly, movement-dependent modulation of these network metrics are significantly correlated with hemibody unified PD rating scales (UPDRS), providing network-level perspectives of the pallidocortical motor network pertaining to PD symptoms (p < 0.05). Significance. Findings in the present study provide network-level understanding of neuronal mechanisms in the pallidocortical motor network underlying PD. It is also highly plausible that the demonstrated approach can be applied in other important subcircuits towards a comprehensive understanding of the BGTC motor network.

Pallidal stimulation in Parkinson disease differentially modulates local and network β activity

β hypersynchrony within the basal ganglia-thalamocortical (BGTC) network has been suggested as a hallmark of Parkinson disease (PD) pathophysiology. Subthalamic nucleus (STN)-DBS has been shown to alter cortical-subcortical synchronization. It is unclear whether this is a generalizable phenomenon of therapeutic stimulation across targets. Objectives. We aimed to evaluate whether DBS of the globus pallidus internus (GPi) results in cortical-subcortical desynchronization, despite the lack of monosynaptic connections between GPi and sensorimotor cortex. Approach. We recorded local field potentials from the GPi and electrocorticographic signals from the ipsilateral sensorimotor cortex, off medications in nine PD patients, undergoing DBS implantation. We analyzed both local oscillatory power and functional connectivity (coherence and debiased weighted phase lag index (dWPLI)) with and without stimulation while subjects were resting with eyes open. Main results. DBS significantly suppressed low β power within the GPi (−26.98% ± 15.14%), p < 0.05) without modulation of sensorimotor cortical β power (low or high). In contrast, stimulation suppressed pallidocortical high β coherence (−38.89% ± 6.19%, p = 0.02) and dWPLI (−61.40% ± 8.75%, p = 0.02). Changes in cortical-subcortical functional connectivity were spatially specific to the motor cortex. Significance. We highlight the role of DBS in desynchronizing network activity, particularly in the high β band. The current study of GPi-DBS suggests these network-level effects are not necessarily dependent and potentially may be independent of the hyperdirect pathway. Importantly, these results draw a sharp distinction between the potential significance of low β oscillations locally within the basal ganglia and high β oscillations across the BGTC motor circuit.

A Common Function of Basal Ganglia-Cortical Circuits Subserving Speed in Both Motor and Cognitive Domains.

Distinct regions of the frontal cortex connect with their basal ganglia and thalamic counterparts, constituting largely segregated basal ganglia-thalamo-cortical (BTC) circuits. However, any common role of the BTC circuits in different behavioral domains remains unclear. Indeed, whether dysfunctional motor and cognitive BTC circuits are responsible for motor slowing and cognitive slowing, respectively, in Parkinson’s disease (PD) is a matter of debate. Here, we used an effortful behavioral paradigm in which the effects of task rate on accuracy were tested in movement, imagery, and calculation tasks in humans. Using nonlinear fitting, we separated baseline accuracy (Abase) and “agility” (ability to function quickly) components of performance in healthy participants and then confirmed reduced agility and preserved Abase for the three tasks in PD. Using functional magnetic resonance imaging (fMRI) and diffusion tractography, we explored the neural substrates underlying speeded performance of the three tasks in healthy participants, suggesting the involvement of distinct BTC circuits in cognitive and motor agility. Language and motor BTC circuits were specifically active during speeded performance of the calculation and movement tasks, respectively, whereas premotor BTC circuits revealed activity for speeded performance of all tasks. Finally, PD showed reduced task rate-correlated activity in the language BTC circuits for speeded calculation, in the premotor BTC circuit for speeded imagery, and in the motor BTC circuits for speeded movement, as compared with controls. The present study casts light on the anatomo-functional organization of the BTC circuits and their parallel roles in invigorating movement and cognition through a function of dopamine.

When will a stuttering moment occur? The determining role of speech motor preparation

The present study aimed to evaluate whether increased activity related to speech motor preparation preceding fluently produced words reflects a successful compensation strategy in stuttering. For this purpose, a contingent negative variation (CNV) was evoked during a picture naming task and measured by use of electro-encephalography. A CNV is a slow, negative event-related potential known to reflect motor preparation generated by the basal ganglia-thalamo-cortical (BGTC) – loop. In a previous analysis, the CNV of 25 adults with developmental stuttering (AWS) was significantly increased, especially over the right hemisphere, compared to the CNV of 35 fluent speakers (FS) when both groups were speaking fluently (Vanhoutte et al., (2015) doi: 10.1016/j.neuropsychologia.2015.05.013). To elucidate whether this increase is a compensation strategy enabling fluent speech in AWS, the present analysis evaluated the CNV of 7 AWS who stuttered during this picture naming task. The CNV preceding AWS stuttered words was statistically compared to the CNV preceding AWS fluent words and FS fluent words.Though no difference emerged between the CNV of the AWS stuttered words and the FS fluent words, a significant reduction was observed when comparing the CNV preceding AWS stuttered words to the CNV preceding AWS fluent words. The latter seems to confirm the compensation hypothesis: the increased CNV prior to AWS fluent words is a successful compensation strategy, especially when it occurs over the right hemisphere. The words are produced fluently because of an enlarged activity during speech motor preparation. The left CNV preceding AWS stuttered words correlated negatively with stuttering frequency and severity suggestive for a link between the left BGTC – network and the stuttering pathology. Overall, speech motor preparatory activity generated by the BGTC – loop seems to have a determining role in stuttering. An important divergence between left and right hemisphere is hypothesized.

Relation between functional connectivity and rhythm discrimination in children who do and do not stutter.

Our ability to perceive and produce rhythmic patterns in the environment supports fundamental human capacities ranging from music and language processing to the coordination of action. This article considers whether spontaneous correlated brain activity within a basal ganglia-thalamocortical (rhythm) network is associated with individual differences in auditory rhythm discrimination. Moreover, do children who stutter with demonstrated deficits in rhythm perception have weaker links between rhythm network functional connectivity and rhythm discrimination? All children in the study underwent a resting-state fMRI session, from which functional connectivity measures within the rhythm network were extracted from spontaneous brain activity. In a separate session, the same children completed an auditory rhythm-discrimination task, where behavioral performance was assessed using signal detection analysis. We hypothesized that in typically developing children, rhythm network functional connectivity would be associated with behavioral performance on the rhythm discrimination task, but that this relationship would be attenuated in children who stutter. Results supported our hypotheses, lending strong support for the view that (1) children who stutter have weaker rhythm network connectivity and (2) the lack of a relation between rhythm network connectivity and rhythm discrimination in children who stutter may be an important contributing factor to the etiology of stuttering.

A computational model of interconnected basal ganglia-thalamocortical loops for goal directed action sequences

The basal ganglia (BG) are a group of subcortical nuclei which are believed to be involved in mediating action selection [1]. They are arranged in a series of topographically organised anatomical ‘loops,’ receiving input from large regions of cortex, and projecting back to the same cortical regions via thalamus. These basal ganglia-thalamocortical (BGTC) loops are widely accepted to be largely segregated. However, increasing anatomical evidence suggests that while this general topography holds, there is significant interconnectivity between loops [2]. This results in a predominantly hierarchical flow of information from regions of cortex and BG associated with motivational processing, through cognitive, and finally to motor regions. This organisation suggests a mechanism by which goal related and contextual information may bias processing in circuits associated with motor actions. We present a model of two BGTC loops which exploits this inter-loop connectivity to integrate several types of information required for the production of goal directed action sequences. An ‘associative loop’ comprising prefrontal cortex (PFC) and its corresponding regions of BG receives information regarding the current goal. By integrating this with stored knowledge of a relevant goal directed action sequence, the loop forms a unique, self-sustaining representation of the temporal task context which indicates the current stage in the ongoing task. A lower ‘motor loop’ is responsible for action selection based on affordance information regarding the objects in the environment available to it. Processing in this loop is influenced by the contextual representation in PFC via corticostriatal connectivity linking the two loops. Under reinforcement learning, these projections adopt the appropriate connectivity to successfully bias contextually appropriate action selection in the motor loop. Changes to the environment as a result of the action selected by the model initiate new representations in PFC, subsequently biasing further action selection, and thereby generating sequential behaviours. The self sustaining nature of prefrontal representations allows the model to function with phasic, rather than sustained feedback signals regarding the action just performed. Four actions – A, B, C and D – are available for selection. The extended sequences ABACAC and ADCACAC are required to achieve goals 1 and 2, respectively. The model is able to consistently execute the required sequences. These results indicate the utility of the BGTC architecture in generating flexible behaviours, in which component actions may be recruited: i) towards multiple goals; ii) as part of distinct sequences; iii) independently of the action just performed; and iv) multiple times in a single sequence. Observed action switching times of approximately 200ms are comparable with existing primate behavioural and neurophysiological data [3], and are an emergent property of the biologically constrained time constants and architecture employed. These results have significant implications for the proposed integrative function of BGTC interconnectivity, and its role in organising sophisticated, contextually appropriate action selection.

Are anticorrelated networks in the brain relevant to schizophrenia?

Most models of schizophrenia are based on basal ganglia-thalamocortical (BGTC) neuronal circuits or brain structures that project to them. Two new neuronal networks have been described which include many of the brain regions associated with BGTC neuronal circuits. These networks have been characterized with a new brain-imaging technique based on low-frequency fluctuations of the blood oxygen level-dependent (BOLD) signal. The new network associated with attention-demanding tasks is referred to as the task-related network and the network associated with stimulus-independent thought during the resting state is referred to as the default network. The 2 networks have been proposed to be negatively correlated or anticorrelated. This article critically reviews the rationale for these anticorrelated networks, the technique with which they are characterized, and preliminary findings in schizophrenia and other neuropsychiatric disorders. Regions associated with the default network overlap with regions important in motivation and are activated by memory retrieval, auditory hallucinations, and ketamine. Task-related networks are necessary for performance of neurocognitive tasks on which schizophrenic patients often perform poorly. It is concluded that anticorrelated networks can be viewed as complementary ways of understanding self-monitoring and task performance which extend present models of schizophrenia based on BGTC circuits. However, there are some limitations with regard the present understanding of brain structures involved in self-monitoring and the lack of asymmetry in the network which may mediate stimulus-independent thought. Further investigations of the default network assessed by low-frequency fluctuations in the BOLD signal seem warranted.