Constraints on the subsecond modulation of striatal dynamics by physiological dopamine signaling.

Dopaminergic neurons play a crucial role in associative learning, but their capacity to regulate behavior on subsecond timescales remains debated. It is thought that dopaminergic neurons drive certain behaviors by rapidly modulating striatal spiking activity; however, a view has emerged that only artificially high (that is, supra-physiological) dopamine signals alter behavior on fast timescales. This raises the possibility that moment-to-moment striatal spiking activity is not strongly shaped by dopamine signals in the physiological range. To test this, we transiently altered dopamine levels while monitoring spiking responses in the ventral striatum of behaving mice. These manipulations led to only weak changes in striatal activity, except when dopamine release exceeded reward-matched levels. These findings suggest that dopaminergic neurons normally play a minor role in the subsecond modulation of striatal dynamics in relation to other inputs and demonstrate the importance of discerning dopaminergic neuron contributions to brain function under physiological and potentially nonphysiological conditions.

Longitudinal Imaging of Reading and Naming Recovery after Stroke.

BACKGROUND: Functional neuroimaging techniques can provide a unique window into the neural basis of language recovery after a stroke. The functional neuroimaging literature on post-stroke language recovery is complex; multiple factors such as the time post-stroke, degree of initial impairment, nature of the task, and lesion location and size, influence recovery patterns. Some of these factors may not be applicable across different stroke participants, and therefore, influence recovery trajectories in vastly different manners across patients. AIMS: The aim of this paper is to examine longitudinal changes in brain activation patterns of reading and naming recovery in participants with posterior cerebral artery (PCA) strokes with varying degrees of initial language impairment. METHODS & PROCEDURES: Five participants with PCA strokes and 5 healthy controls underwent language testing and functional MRI with a covert reading task and an overt picture-naming task. Stroke participants underwent language testing and scanning at the three time points: 2-5 weeks (T1, subacute phase), 4-7 months (T2, chronic phase), and 11-13 months (T3, chronic phase). Healthy controls underwent language testing and fMRI once. OUTCOMES & RESULTS: Language testing indicated that there were varying degrees of reading and naming recovery or decline from the subacute to the chronic phase. With regard to task-based fMRI, we found that for most participants, naming consistently activated a diffuse bilateral network of frontal, temporal, parietal, and occipital regions across the three time points. In contrast, for the reading task, functional activation across the three time points was more left lateralized with a right to left shift in peak activation from the subacute to the chronic phase. CONCLUSIONS: These results indicate that the patterns of activation during language processing is highly dependent on the task and phase of recovery, and these results may have implications for neurally targeted non-invasive brain stimulation techniques.

Imaging network level language recovery after left PCA stroke.

PURPOSE: The neural mechanisms that support aphasia recovery are not yet fully understood. Our goal was to evaluate longitudinal changes in naming recovery in participants with posterior cerebral artery (PCA) stroke using a case-by-case analysis. METHODS: Using task based and resting state functional magnetic resonance imaging (fMRI) and detailed language testing, we longitudinally studied the recovery of the naming network in four participants with PCA stroke with naming deficits at the acute (0 week), sub acute (3-5 weeks), and chronic time point (5-7 months) post stroke. Behavioral and imaging analyses (task related and resting state functional connectivity) were carried out to elucidate longitudinal changes in naming recovery. RESULTS: Behavioral and imaging analysis revealed that an improvement in naming accuracy from the acute to the chronic stage was reflected by increased connectivity within and between left and right hemisphere "language" regions. One participant who had persistent moderate naming deficit showed weak and decreasing connectivity longitudinally within and between left and right hemisphere language regions. CONCLUSIONS: These findings emphasize a network view of aphasia recovery, and show that the degree of inter- and intra- hemispheric balance between the language-specific regions is necessary for optimal recovery of naming, at least in participants with PCA stroke.

Cerebellar tDCS: A Novel Approach to Augment Language Treatment Post-stroke.

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, double-blind, sham controlled within-subject crossover trial. We also investigated changes in functional connectivity using resting state functional magnetic resonance imaging before and 2 months post-treatment. Both anodal and sham treatments resulted in improved spelling to dictation for trained and untrained words immediately after and 2 months post-treatment. However, there was greater improvement with tDCS than with sham, especially for untrained words. Further, generalization to written picture naming was only noted during tDCS but not with sham. The resting state functional connectivity data indicate that improvement in spelling was accompanied by an increase in cerebro-cerebellar network connectivity. These results highlight the therapeutic potential of right cerebellar tDCS to augment spelling therapy in an individual with large bilateral chronic strokes.