Georgina M. Jackson

Enhanced cognitive control in young people with Tourette's syndrome.

Tourettes syndrome (TS) is a neurodevelopmental disorder characterized by the presence of chronic vocal and motor tics. Tics are sudden, highly stereotyped, movements that can be simple or complex in appearance. Since patients with TS have difficulties preventing unwanted movements, one might expect that their ability to voluntarily control goal-directed movements would be similarly poor. Indeed, it has been suggested that TS sufferers are impaired at inhibiting reflexively triggered movements and in rapidly selecting or switching between different motor sets. This idea is consistent with current views on the neurological basis of TS that posit a dysfunction of the neural circuits linking the frontal lobes and the striatum. These circuits are known to be involved in the voluntary control of action. By using an oculomotor switching task, we show for the first time that young people with TS exhibit paradoxically greater levels of cognitive control over their movements than their age-matched controls. This finding is consistent with an increased need to monitor and control movements and may indicate a subcortical locus for the triggering of tics. It also suggests that the constant need to suppress tics could have resulted in an enhancement of the executive processes involved in inhibitory control.

Are non-relevant objects represented in working memory? The effect of non-target objects on reach and grasp kinematics

The role of visual information and the precise nature of the representations used in the control of prehension movements has frequently been studied by having subjects reach for target objects in the absence of visual information. Such manipulations have often been described as preventing visual feedback; however, they also impose a working memory load not found in prehension movements with normal vision. In this study we examined the relationship between working memory and visuospatial attention using a prehension task. In this study six healthy, right-handed adult subjects reached for a wooden block under conditions of normal vision, or else with their eyes closed having first observed the placement of the target. Furthermore, the role of visuospatial attention was examined by studying the effect, on transport and grasp kinematics, of placing task-irrelevant “flanker” objects (a wooden cylinder) within the visual field on a proportion of trials. Our results clearly demonstrated that the position of flankers produced clear interference effects on both transport and grasp kinematics. Furthermore, interference effects were significantly greater when subjects reached to the remembered location of the target (i.e., with eyes closed). The finding that the position of flanker objects influences both transport and grasp components of the prehension movement is taken as support for the view that these components may not be independently computed and that subjects may prepare a coordinated movement in which both transport and grasp are specifically adapted to the task in hand. The finding that flanker effects occur primarily when reaching to the remembered location of the target object is interpreted as supporting the view that attentional processes do not work efficiently on working memory representations.

Compensatory Neural Reorganization in Tourette Syndrome

Summary Children with neurological disorders may follow unique developmental trajectories whereby they undergo compensatory neuroplastic changes in brain structure and function that help them gain control over their symptoms [1–6]. We used behavioral and brain imaging techniques to investigate this conjecture in children with Tourette syndrome (TS). Using a behavioral task that induces high levels of intermanual conflict, we show that individuals with TS exhibit enhanced control of motor output. Then, using structural (diffusion-weighted imaging) brain imaging techniques, we demonstrate widespread differences in the white matter (WM) microstructure of the TS brain that include alterations in the corpus callosum and forceps minor (FM) WM that significantly predict tic severity in TS. Most importantly, we show that task performance for the TS group (but not for controls) is strongly predicted by the WM microstructure of the FM pathways that lead to the prefrontal cortex and by the functional magnetic resonance imaging blood oxygen level-dependent response in prefrontal areas connected by these tracts. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.

Enhanced cognitive control in Tourette Syndrome during task uncertainty

Tourette Syndrome (TS) is a developmental neurological condition that is characterised by the presence of multiple motor and one or more vocal tics. Tics are highly stereotyped repetitive behaviours that fluctuate in type, complexity and severity. TS has been linked to impaired cognitive control processes, however, a recent study (Mueller et al. in Curr Biol 16:570–573, 2006) demonstrated that young people with TS, although exhibiting chronic motor and vocal tics, nevertheless performed significantly better than a group of age-matched controls on a task that required extremely high levels of cognitive control (i.e., predictably shifting between executing pro-saccade and anti-saccade responses to a visual stimulus). As predictable task sequences allow task-related cognitive processes to commence prior to the presentation of target stimuli we examined whether the superior performance of the TS group could be replicated when task sequences were varied unpredictably. Our results confirmed that both the TS group and an age-matched control group benefited, by the same extent, when the saccade task (pro-saccade vs. anti-saccade) was pre-cued. In contrast, while the control group showed a significant decrease in performance on task switch trials relative to task repetition trials—the TS group exhibited no significant ‘costs’ of switching task. While task performance was modulated by response and target location shifts in the control group, these factors had less impact on the TS group’s performance on task switch trials. These results confirm and extend the previous demonstration that individuals with TS exhibit paradoxically greater levels of cognitive control than healthy controls.

Cognitive deficits in early-onset schizophrenia spectrum patients and their non-psychotic siblings: A comparison with ADHD

BACKGROUND Previous research has shown cognitive deficits in patients with schizophrenia spectrum disorders in the areas of executive function, verbal memory and attention. Subtle deficits have been shown in healthy first-degree relatives of patients, suggesting that they may be trait markers. The specificity of these markers for schizophrenia compared with another neurodevelopmental disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably established. METHODS The Rey Auditory Verbal Learning Test (RAVLT), Hayling Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS) and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC; n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27). RESULTS The SZ group were impaired on all measures. The SZ-SIB group were impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response initiation (HSCT); error rates for the FAS and HSCT. There were no significant differences between the SZ-SIB and ADHD groups on individual measures of cognitive function. Principal Components Analysis revealed four factors on which further analyses were conducted. The SZ-SIB and ADHD groups showed different profiles of impairment on components related to response initiation and sustained attention/vigilance when each was compared with the HC group. CONCLUSIONS Deficits in intellectual function, verbal memory and response initiation/inhibition were found in the SZ-SIB group indicating that these are markers of risk for schizophrenia. Subtle differences in profiles of impairment in the SZ-SIB and ADHD groups on composite measures of attention and response initiation require further investigation.

The internal control of action and Parkinson's disease: a kinematic analysis of visually-guided and memory-guided prehension movements

This paper reports two experiments which examined the effects of Parkinsons disease (PD) upon the sensorimotor mechanisms used to control prehension movements. Transport and grasp kinematics for visually-guided and memory-guided prehension movements were examined in healthy control subjects and compared against those of patients with idiopathic PD. Two research questions were addressed: (1) Are patients with PD particularly susceptible to distraction by non-relevant objects? (2) Are patients with PD especially reliant on external feedback when executing goal-directed actions? The results indicated that the patient group were no more susceptible to distraction by non-relevant objects than the control group. In contrast, the patients with PD were shown to be significantly, impaired when executing memory-guided reaches. Furthermore, the deficits exhibited by the PD group on memory-guided reaches were confined solely to those markers associated with the transport component of the prehension movement. That is, while both controls and patients with PD widened their grip aperture on memory-guided trials, the magnitude of this adjustment was comparable across the two groups. The implications of these findings for theories of visuomotor processing in sufferers of PD and the control of prehension movements more generally are discussed.

ERP correlates of a receptive language-switching task

Previous research has shown large response time costs (in excess of 50 ms) when bilingual speakers switch predictably back and forth between naming items (a productive switching task) in their first (L1) and second languages (L2). A recent study using event-related potentials (ERPs) has shown that switching between languages is associated with activity over frontal (N2) and parietal (late positive complex) areas of cortex (Jackson, Swainson, Cunnington, & Jackson, 2001). Switching between naming in different languages requires a switch in both language representations and language-specific motor responses. The current study investigated a receptive (input) language-switching task with a common manual response. Number words were presented in L1 and L2, and participants were required to judge whether the words were odd or even (a parity judgement). Response costs were considerably reduced, and the frontal and parietal switch related activity reported in the productive switching task was absent. Receptive switching was associated with early switch-related activity over central sensors that were not language specific. These results are discussed in relation to the idea that there is no language-specific lexical selection mechanism. Instead the costs of receptive language switching may arise from outside the bilingual lexicon.

Increased GABA Contributes to Enhanced Control over Motor Excitability in Tourette Syndrome

Summary Tourette syndrome (TS) is a developmental neurological disorder characterized by vocal and motor tics [1] and associated with cortical-striatal-thalamic-cortical circuit dysfunction [2, 3], hyperexcitability within cortical motor areas [4], and altered intracortical inhibition [4–7]. TS often follows a developmental time course in which tics become increasingly more controlled during adolescence in many individuals [1], who exhibit enhanced control over their volitional movements [8–11]. Importantly, control over motor outputs appears to be brought about by a reduction in the gain of motor excitability [6, 7, 12, 13]. Here we present a neurochemical basis for a localized gain control mechanism. We used ultra-high-field (7 T) magnetic resonance spectroscopy to investigate in vivo concentrations of γ-aminobutyric acid (GABA) within primary and secondary motor areas of individuals with TS. We demonstrate that GABA concentrations within the supplementary motor area (SMA)—a region strongly associated with the genesis of motor tics in TS [14]—are paradoxically elevated in individuals with TS and inversely related to fMRI blood oxygen level-dependent activation. By contrast, GABA concentrations in control sites do not differ from those of a matched control group. Importantly, we also show that GABA concentrations within the SMA are inversely correlated with cortical excitability in primary motor cortex and are predicted by motor tic severity and white-matter microstructure (FA) within a region of the corpus callosum that projects to the SMA within each hemisphere. Based upon these findings, we propose that extrasynaptic GABA contributes to a form of control, based upon localized tonic inhibition within the SMA, that may lead to the suppression of tics.

Event-related potentials in adolescents with schizophrenia and their siblings: a comparison with attention-deficit/hyperactivity disorder.

BACKGROUND Identifying trait markers specific to schizophrenia might uncover mechanisms underlying illness susceptibility. Previous research shows the N2 and P3 event-related potentials are abnormal in schizophrenia; specificity of these potential trait markers has not been well established. METHODS Electroencephalogram data were recorded from four adolescent groups: early-onset schizophrenia patients (SZ; n = 30); non-psychotic siblings of schizophrenia patients (SZ-SIB; n = 36); healthy control subjects (HC; n = 36); a neurodevelopmental attention-deficit/hyperactivity disorder (ADHD) comparison group (n = 27), during auditory oddball and visual go/no-go tasks. The P3 was measured to targets in the oddball task. The N2 and P3 were measured to go and no-go stimuli in the go/no-go task. RESULTS Compared with the HC group, the SZ and SZ-SIB groups showed significantly reduced auditory oddball P3 amplitude. Visual P3 amplitude was significantly reduced in the SZ group for no-go stimuli and the SZ-SIB group for go and no-go stimuli. The P3 amplitude in the ADHD group was not significantly reduced for either paradigm. The SZ and ADHD groups showed significantly reduced N2 amplitude in the go/no-go task; the SZ-SIB group was not significantly different from the HC group. CONCLUSIONS Results revealed reduced P3 amplitude in schizophrenia patients and adolescent non-psychotic siblings in an auditory oddball and a visual go/no-go task. The SZ-SIB and ADHD groups showed a different ERP profile when each was compared with the HC group: siblings showed reduced P3 amplitude in both tasks and normal N2 in the go/no-go task; the opposite pattern was observed in the ADHD group.

Cognitive control over motor output in Tourette syndrome

Tourette syndrome [TS] is a neurodevelopmental disorder characterised by chronic vocal and motor tics. TS has been associated with dysfunctional cognitive (inhibitory) control of behaviour, however the evidence for this, beyond the occurrence of tics, is scant. Furthermore, in recent studies of uncomplicated TS, it has been shown that adolescents with TS exhibit paradoxically enhanced cognitive control of motor output, consistent with the typical developmental profile of increasing control of tics during adolescence. Here we present arguments, together with new data, that run counter to the widely held view that prefrontal cortex (PFC) is the source of inhibitory task-control signals. Instead, we argue that PFC should be viewed as a source of facilitatory signals that bias competition in brain areas more directly involved in motor execution. Importantly, we argue that in TS, over-activation of PFC may contribute to the hyper-excitability of motor regions and the occurrence of tics; and that compensatory changes, leading to enhanced cognitive control in TS, may primarily be implemented by distributed changes in local cortical excitability.