OBJECTIVE: This review aims to rediscuss the leading theories concerning the role of basal ganglia and the thalamus in the genesis of aphasic symptoms in the absence of gross anatomical lesions in cortical language areas as assessed by conventional neuroimaging studies.
RESULTS: New concepts in language processing and modern neuroimaging techniques have enabled some progress in resolving the impasse between the current dominant theories: (a) direct and specific linguistic processing and (b) subcortical structures as processing relays in domain-general functions. Of particular interest are studies of connectivity based on functional magnetic resonance imaging (MRI) and tractography that highlight the impact of white matter pathway lesions on aphasia development and recovery. Connectivity studies have put into evidence the central role of the arcuate fasciculus (AF), inferior frontal occipital fasciculus (IFOF), and uncinate fasciculus (UF) in the genesis of aphasia. Regarding the thalamus, its involvement in lexical-semantic processing through modulation of the frontal cortex is becoming increasingly apparent.

Prior studies have documented the role of the striatum and its dopaminergic input in time processing, but the contribution of local striatal cholinergic innervation has not been specifically investigated. To address this issue, we recorded the activity of tonically active neurons (TANs), thought to be cholinergic interneurons in the striatum, in two male macaques performing self-initiated movements after specified intervals in the seconds range have elapsed. The behavioral data showed that movement timing was adjusted according to the temporal requirements. About one-third of all recorded TANs displayed brief depressions in firing in response to the cue that indicates the interval duration, and the strength of these modulations was, in some instances, related to the timing of movement. The rewarding outcome of actions also impacted TAN activity, as reflected by stronger responses to the cue paralleled by weaker responses to reward when monkeys performed correctly timed movements over consecutive trials. It therefore appears that TAN responses may act as a start signal for keeping track of time and reward prediction could be incorporated in this signaling function. We conclude that the role of the striatal cholinergic TAN system in time processing is embedded in predicting rewarding outcomes during timing behavior.

BACKGROUND: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson\'s disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally.
METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum.
RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group.
CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.

Using delay differential equations to study mathematical models of Parkinson\'s disease and Huntington\'s disease is important to show how important it is for synchronization between basal ganglia loops to work together. We used the delay circuit RLC (resistor, inductor, capacitor) model to show how the direct pathway and the indirect pathway in the basal ganglia excite and inhibit the motor cortex, respectively. A term has been added to the mathematical model without time delay in the case of the hyperdirect pathway. It is proposed to add a non-linear term to adjust the synchronization. We studied Hopf bifurcation conditions for the proposed models. The desynchronization of response times between the direct pathway and the indirect pathway leads to different symptoms of Parkinson\'s disease. Tremor appears when the response time in the indirect pathway increases at rest. The simulation confirmed that tremor occurs and the motor cortex is in an inhibited state. The direct pathway can increase the time delay in the dopaminergic pathway, which significantly increases the activity of the motor cortex. The hyperdirect pathway regulates the activity of the motor cortex. The simulation showed bradykinesia occurs when we switch from one movement to another that is less exciting for the motor cortex. A decrease of GABA in the striatum or delayed excitation of the substantia nigra from the subthalamus may be a major cause of Parkinson\'s disease. An increase in the response time delay in one of the pathways results in the chaotic movement characteristic of Huntington\'s disease.

Background and Objectives: This study was performed for the purpose of assessing whether antiepileptic levetiracetam treatment produces a change in brain volumes in children with epilepsy. To that end, we compared the volumes of the basal ganglia (caudate nucleus, putamen, globus, hip-pocampus, and thalamus) at magnetic resonance imaging (MRI) before and after treatment (months 18-24) in pediatric epilepsy patients using levetiracetam. Materials and Methods: This retrospective study involved a volumetric comparison of patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic between 01.08.2019 and 01.11.2023 and diagnosed with epilepsy, and who underwent cranial MRI before and 18-24 months after treatment at the radiology department. The demographic and clinical characteristics (age, sex, family history of epilepsy, type of epilepsy, and EEG features (normal, abnormal, epileptiform)) of the patients included in the study were recorded. Results: The comparison of basal ganglia volumes at cranial MRI before and at months 18-24 of treatment revealed significant differences in the left caudate nucleus, right putamen, left putamen, left globus pallidus, right thalamus, left thalamus, and right hippocampal regions. Conclusions: In conclusion, differing findings are encountered at cranial imaging in patients with epilepsy, depending on the seizure frequency, activity, and the type of antiepileptic drugs used. This study compared basal ganglia volumes on cranial MRIs taken before and 18-24 months after treatment in pediatric epilepsy patients using levetiracetam. A significant increase was observed in the volumes of basal ganglia (caudate nucleus, putamen, globus pallidus, hippocampus, and thalamus) on the MRIs of pediatric epilepsy patients using levetiracetam.

BACKGROUND: Studies have demonstrated the potential of repetitive transcranial magnetic stimulation (rTMS) to decrease smoking cravings in individuals with tobacco use disorder (TUD). However, the neural features underlying the effects of rTMS treatment, especially the dynamic attributes of brain networks associated with the treatment, remain unclear.
METHODS: Using dynamic functional connectivity analysis, this study first explored the differences in dynamic functional network features between 60 subjects with TUD and 64 nonsmoking healthy controls (HCs). Then, the left dorsolateral prefrontal cortex (DLPFC) was targeted for a five-day course of rTMS treatment in the 60 subjects with TUD (active rTMS in 42 subjects and sham treatment in 18 subjects). We explored the effect of rTMS on the dynamic network features associated with rTMS by comparing the actively treated group and the sham group.
RESULTS: Compared to nonsmokers, TUD subjects exhibited an increased integration coefficient between the frontoparietal network (FPN) and the basal ganglia network (BGN) and a reduced integration coefficient between the medial frontal network (MFN) and the FPN. Analysis of variance revealed that rTMS treatment reduced the integration coefficient between the FPN and BGN and improved the recruitment coefficient of the FPN.
CONCLUSIONS: This study involved a limited sample of young male smokers, and the findings may not generalize to older smokers or female smokers with an extensive history of smoking.
CONCLUSIONS: rTMS treatment of the left DLPFC exhibited significant effectiveness in restructuring the neural circuits associated with TUD while significantly mitigating smoking cravings.

UNASSIGNED: The dichotomy between the hypo- versus hyperkinetic nature of Parkinson\'s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.
UNASSIGNED: Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials.
UNASSIGNED: GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression.
UNASSIGNED: We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.
UNASSIGNED: This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).

Mammalian functional architecture flexibly adapts, transitioning from integration where information is distributed across the cortex, to segregation where information is focal in densely connected communities of brain regions. This flexibility in cortical brain networks is hypothesized to be driven by control signals originating from subcortical pathways, with the basal ganglia shifting the cortex towards integrated processing states and the cerebellum towards segregated states. In a sample of healthy human participants (N=242), we used fMRI to measure temporal variation in global brain networks while participants performed two tasks with similar cognitive demands (Stroop and Multi-Source Inference Task (MSIT)). Using the modularity index, we determined cortical networks shifted from integration (low modularity) at rest to high modularity during easier i.e. congruent (segregation). Increased task difficulty (incongruent) resulted in lower modularity in comparison to the easier counterpart indicating more integration of the cortical network. Influence of basal ganglia and cerebellum was measured using eigenvector centrality. Results correlated with decreases and increases in cortical modularity respectively, with only the basal ganglia influence preceding cortical integration. Our results support the theory the basal ganglia shifts cortical networks to integrated states due to environmental demand. Cerebellar influence correlates with shifts to segregated cortical states, though may not play a causal role.

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion\'s direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8-10 days, striatal projection and interneuronal dynamics did not-eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics.

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this manuscript, we use in vivo optogenetics to show that a projection-defined neural subpopulation within each structure exerts non-canonical effects on locomotion. These non-canonical subpopulations are defined by their projection to the pedunculopontine nucleus (PPN) and mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence.