Temporal discrimination: Mechanisms and relevance to adult-onset dystonia

Temporal discrimination is the ability to determine that two sequential sensory stimuli are separated in time. For any individual, the temporal discrimination threshold (TDT) is the minimum interval at which paired sequential stimuli are perceived as being asynchronous; this can be assessed, with high test-retest and inter-rater reliability, using a simple psychophysical test. Temporal discrimination is disordered in a number of basal ganglia diseases including adult-onset dystonia, of which the two most common phenotypes are cervical dystonia and blepharospasm. The causes of adult-onset focal dystonia are unknown; genetic, epigenetic, and environmental factors are relevant. Abnormal TDTs in adult-onset dystonia are associated with structural and neurophysiological changes considered to reflect defective inhibitory interneuronal processing within a network which includes the superior colliculus, basal ganglia, and primary somatosensory cortex. It is hypothesized that abnormal temporal discrimination is a mediational endophenotype and, when present in unaffected relatives of patients with adult-onset dystonia, indicates non-manifesting gene carriage. Using the mediational endophenotype concept, etiological factors in adult-onset dystonia may be examined including (i) the role of environmental exposures in disease penetrance and expression; (ii) sexual dimorphism in sex ratios at age of onset; (iii) the pathogenesis of non-motor symptoms of adult-onset dystonia; and (iv) subcortical mechanisms in disease pathogenesis

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies

Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Oscillatory multiplexing of neural population codes for interval timing and working memory

Interval timing and working memory are critical components of cognition that are supported by neural oscillations in prefrontal-striatal-hippocampal circuits. In this review, the properties of interval timing and working memory are explored in terms of behavioral, anatomical, pharmacological, and neurophysiological findings. We then describe the various neurobiological theories that have been developed to explain these cognitive processes - largely independent of each other. Following this, a coupled excitatory - inhibitory oscillation (EIO) model of temporal processing is proposed to address the shared oscillatory properties of interval timing and working memory. Using this integrative approach, we describe a hybrid model explaining how interval timing and working memory can originate from the same oscillatory processes, but differ in terms of which dimension of the neural oscillation is utilized for the extraction of item, temporal order, and duration information. This extension of the striatal beat-frequency (SBF) model of interval timing (Matell and Meck, 2000, 2004) is based on prefrontal-striatal-hippocampal circuit dynamics and has direct relevance to the pathophysiological distortions observed in time perception and working memory in a variety of psychiatric and neurological conditions. (C) 2014 Elsevier Ltd. All rights reserved.</p

Finding rhythm through auditory imagery: an approach to Parkinson’s Disease treatment

The following research article explores music therapy in the treatment of Parkinson’s Disease (PD). The general interaction between the rhythmic properties of music and motor associated brain areas is discussed at length. These interactions provide a basis for understanding how music therapy can address the rhythmic impairments of the disease. Dance therapy, Musical Sonification, Rhythmic Auditory Stimulation (RAS) are three types of music-based therapies that have been found to be effective in treating the motor symptoms of PD. These therapies may be particularly effective for the PD population because they draw upon musical rhythm as an external pacing cue.While external pacing cues have been found to help PD patients entrain to rhythm, research has not yet explored how rhythm can be internalized over time. The current article proposes that the experience of Involuntary Musical Imagery (INMI) may offer patients a means of creating an internalized representation of rhythm that can be maintained beyond the therapeutic setting. Strategies to increase the occurrence of INMI are explored, accounting for individual differences and certain musical characteristics. In addition to advocating for music-based therapies in the treatment of PD, there also calls for increased research on how INMI may be incorporated into these therapies