Fast Intracortical Sensory-Motor Integration: A Window Into the Pathophysiology of Parkinson’s Disease

Parkinson’s Disease (PD) is a prototypical basal ganglia disorder. Nigrostriatal dopaminergic denervation leads to progressive dysfunction of the cortico-basal ganglia-thalamo-cortical sensorimotor loops, causing the classical motor symptoms. Although the basal ganglia do not receive direct sensory input, they are important for sensorimotor integration. Therefore, the basal ganglia dysfunction in PD may profoundly affect sensory-motor interaction in the cortex. Cortical sensorimotor integration can be probed with transcranial magnetic stimulation (TMS) using a well-established conditioning-test paradigm, called short-latency afferent inhibition (SAI). SAI probes the fast-inhibitory effect of a conditioning peripheral electrical stimulus on the motor response evoked by a TMS test pulse given to the contralateral primary motor cortex (M1). Since SAI occurs at latencies that match the peaks of early cortical somatosensory potentials, the cortical circuitry generating SAI may play an important role in rapid online adjustments of cortical motor output to changes in somatosensory inputs. Here we review the existing studies that have used SAI to examine how PD affects fast cortical sensory-motor integration. Studies of SAI in PD have yielded variable results, showing reduced, normal or even enhanced levels of SAI. This variability may be attributed to the fact that the strength of SAI is influenced by several factors, such as differences in dopaminergic treatment or the clinical phenotype of PD. Inter-individual differences in the expression of SAI has been shown to scale with individual motor impairment as revealed by UPDRS motor score and thus, may reflect the magnitude of dopaminergic neurodegeneration. The magnitude of SAI has also been linked to cognitive dysfunction, and it has been suggested that SAI also reflects cholinergic denervation at the cortical level. Together, the results indicate that SAI is a useful marker of disease-related alterations in fast cortical sensory-motor integration driven by subcortical changes in the dopaminergic and cholinergic system. Since a multitude of neurobiological factors contribute to the magnitude of inhibition, any mechanistic interpretation of SAI changes in PD needs to consider the group characteristics in terms of phenotypical spectrum, disease stage, and medication

Can Transcranial Electrical Stimulation Localize Brain Function?

Transcranial electrical stimulation (TES) uses constant (TDCS) or alternating currents (TACS) to modulate brain activity. Most TES studies apply low-intensity currents through scalp electrodes (≤2 mA) using bipolar electrode arrangements, producing weak electrical fields in the brain (<1 V/m). Low-intensity TES has been employed in humans to induce changes in task performance during or after stimulation. In analogy to focal transcranial magnetic stimulation, TES-induced behavioral effects have often been taken as evidence for a causal involvement of the brain region underlying one of the two stimulation electrodes, often referred to as the active electrode. Here, we critically review the utility of bipolar low-intensity TES to localize human brain function. We summarize physiological substrates that constitute peripheral targets for TES and may mediate subliminal or overtly perceived peripheral stimulation during TES. We argue that peripheral co-stimulation may contribute to the behavioral effects of TES and should be controlled for by “sham” TES. We discuss biophysical properties of TES, which need to be considered, if one wishes to make realistic assumptions about which brain regions were preferentially targeted by TES. Using results from electric field calculations, we evaluate the validity of different strategies that have been used for selective spatial targeting. Finally, we comment on the challenge of adjusting the dose of TES considering dose–response relationships between the weak tissue currents and the physiological effects in targeted cortical areas. These considerations call for caution when attributing behavioral effects during or after low-intensity TES studies to a specific brain region and may facilitate the selection of best practices for future TES studies

Simultaneous Assessment of White Matter Changes in Microstructure and Connectedness in the Blind Brain

Magnetic resonance imaging (MRI) of the human brain has provided converging evidence that visual deprivation induces regional changes in white matter (WM) microstructure. It remains unclear how these changes modify network connections between brain regions. Here we used diffusion-weighted MRI to relate differences in microstructure and structural connectedness of WM in individuals with congenital or late-onset blindness relative to normally sighted controls. Diffusion tensor imaging (DTI) provided voxel-specific microstructural features of the tissue, while anatomical connectivity mapping (ACM) assessed the connectedness of each voxel with the rest of the brain. ACM yielded reduced anatomical connectivity in the corpus callosum in individuals with congenital but not late-onset blindness. ACM did not identify any brain region where blindness resulted in increased anatomical connectivity. DTI revealed widespread microstructural differences as indexed by a reduced regional fractional anisotropy (FA). Blind individuals showed lower FA in the primary visual and the ventral visual processing stream relative to sighted controls regardless of the blindness onset. The results show that visual deprivation shapes WM microstructure and anatomical connectivity, but these changes appear to be spatially dissociated as changes emerge in different WM tracts. They also indicate that regional differences in anatomical connectivity depend on the onset of blindness

Theta Activity in the Left Dorsal Premotor Cortex During Action Re-Evaluation and Motor Reprogramming

The ability to rapidly adjust our actions to changes in the environment is a key function of human motor control. Previous work implicated the dorsal premotor cortex (dPMC) in the up-dating of action plans based on environmental cues. Here we used electroencephalography (EEG) to identify neural signatures of up-dating cue-action relationships in the dPMC and connected frontoparietal areas. Ten healthy subjects performed a pre-cued alternate choice task. Simple geometric shapes cued button presses with the right or left index finger. The shapes of the pre-cue and go-cue differed in two third of trials. In these incongruent trials, the go-cue prompted a re-evaluation of the pre-cued action plan, slowing response time relative to trials with identical cues. This re-evaluation selectively increased theta band activity without modifying activity in alpha and beta band. Source-based analysis revealed a widespread theta increase in dorsal and mesial frontoparietal areas, including dPMC, supplementary motor area (SMA), primary motor and posterior parietal cortices (PPC). Theta activity scaled positively with response slowing and increased more strongly when the pre-cue was invalid and required subjects to select the alternate response. Together, the results indicate that theta activity in dPMC and connected frontoparietal areas is involved in the re-adjustment of cue-induced action tendencies

Risk for affective disorders is associated with greater prefrontal gray matter volumes: A prospective longitudinal study

Background: Major depression and bipolar disorders aggregates in families and are linked with a wide range of neurobiological abnormalities including cortical gray matter (GM) alterations. Prospective studies of individuals at familial risk may expose the neural mechanisms underlying risk transmission. Methods: We used voxel based morphometry to investigate changes in regional GM brain volume, over a seven-year period, in 37 initially healthy individuals having a mono- or di-zygotic twin diagnosed with major depression or bipolar disorder (high-risk group; mean age 41.6yrs.) as compared to 36 individuals with no history of affective disorders in the index twin and first-degree relatives (low-risk group; mean age 38.5yrs.). Results: Groups did not differ in regional GM volume changes over time. However, independent of time, high-risk twins had significantly greater GM volumes in bilateral dorsal anterior cingulate, inferior frontal gyrus and temporoparietal regions as compared to low-risk twins. Further, individuals who developed an affective disorder at follow-up (n=12), had relatively the largest GM volumes, both at baseline and follow-up, in the right dorsal anterior cingulate cortex and right inferior frontal cortex compared to high- and low-risk twins who remained well at follow-up. Conclusion: This pattern of apparently stable grater regional GM volume may constitute a neural marker of an increased risk for developing an affective disorder in individuals at familial risk. Keywords: Affective disorders, Structural MRI, Anterior cingulate cortex, VB

Observing repetitive finger movements modulates response times of auditorily cued finger movements

Our motor and perceptual representations of actions seem to be intimately linked and the human mirror neuron system (MNS) has been proposed as the mediator. In two experiments, we presented biological or non-biological movement stimuli that were either congruent or incongruent to a required response prompted by a tone. When the tone occurred with the onset of the last movement in a series, i.e., it was perceived during the movement presentation, congruent biological stimuli resulted in faster reaction times than congruent non-biological stimuli. The opposite was observed for incongruent stimuli. When the tone was presented after visual movement stimulation, however, no such interaction was present. This implies that biological movement stimuli only affect motor behaviour during visual processing but not thereafter. These data suggest that the MNS is an “online” system; longstanding repetitive visual stimulation (Experiment 1) has no benefit in comparison to only one or two repetitions (Experiment 2)