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Huntington's disease (HD) can impair social cognition. This study investigated whether patients with HD exhibit neural differences to healthy controls when they are considering mental and physical states relating to the static expressions of human eyes. Thirty-two patients with HD and 28 age-matched controls were scanned with fMRI during two versions of the Reading the Mind in the Eyes Task: The standard version requiring mental state judgments, and a comparison version requiring judgments about age. HD was associated with behavioral deficits on only the mental state eyes task. Contrasting the two versions of the eyes task (mental state > age judgment) revealed hypoactivation within left middle frontal gyrus and supramarginal gyrus in HD. Subgroup analyses comparing premanifest HD patients to age-matched controls revealed reduced activity in right supramarginal gyrus and increased activity in anterior cingulate during mental state recognition in these patients, while manifest HD was associated with hypoactivity in left insula and left supramarginal gyrus. When controlling for the effects of healthy aging, manifest patients exhibited declining activation within areas including right temporal pole. Our findings provide compelling evidence for a selective impairment of internal emotional status when patients with HD appraise facial features in order to make social judgements. Differential activity in temporal and anterior cingulate cortices may suggest that poor emotion regulation and emotional egocentricity underlie impaired mental state recognition in premanifest patients, while more extensive mental state recognition impairments in manifest disease reflect dysfunction in neural substrates underlying executive functions, and the experience and interpretation of emotion.

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Transcranial direct current stimulation (tDCS) combined with a cognitive task can enhance targeted aspects of cognitive functioning in clinical populations. The movement disorder Huntington's disease (HD) is associated with progressive cognitive impairment. Deficits in working memory (WM) can be apparent early in the disease and impact functional capacity. We investigated whether tDCS combined with cognitive training could improve WM in patients with HD, and if baseline clinical or cognitive measures may predict efficacy. Twenty participants with HD completed this crossover trial, undergoing 1.5mA anodal tDCS over left dorsolateral prefrontal cortex and sham stimulation on separate visits. Participants and assessor were blinded to condition order, which was randomised across participants. All participants completed baseline clinical and cognitive assessments. Pre- and post-stimulation tasks included digit reordering, computerised n-back tests and a Stroop task. During 15min of tDCS/sham stimulation, participants practiced 1- and 2-back WM tasks. Participants exhibited an increase in WM span on the digit re-ordering span task from pre- to post-stimulation after tDCS, but not after sham stimulation. Gains in WM were positively related to motor symptom ratings and negatively associated with verbal fluency scores. Patients with more severe motor symptoms showed greatest improvement, suggesting that motor symptom ratings may help identify patients who are most likely to benefit from tDCS. CONCLUSIONS: Dorsolateral prefrontal tDCS appears well tolerated in HD and enhances WM span compared to sham stimulation. Our findings strongly encourage further investigation of the extent to which tDCS combined with cognitive training could enhance everyday function in HD. ClinicalTrials.gov; NCT02216474 Brain stimulation in Movement Disorders; https://clinicaltrials.gov/ct2/show/NCT02216474.

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Changes in mental state and behaviour have been acknowledged in Huntington's disease since the original monograph in 1872 provided evidence of disinhibition and impaired social cognition. Behavioural problems can manifest before obvious motor symptoms and are frequently the most disabling part of the illness. Although pharmacological treatments are used routinely for psychiatric difficulties in Huntington's disease, the scientific evidence base for their use is somewhat sparse. Moreover, effective treatments for apathy and cognitive decline do not currently exist. Understanding the social cognitive impairments associated with Huntington's disease can assist management, but related therapeutic interventions are needed. Future research should aim to design rating scales for behaviour and mental state in Huntington's disease that can detect change in clinical trials. Generally, communication and understanding of behaviour and mental state in Huntington's would be enhanced by a clear conceptual framework that unifies ideas around movement, cognition, emotion, behaviour, and mental state, reflecting both the experience of the patient and their underlying neuropathology.

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Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics, repetitive movements and vocalizations which are prompted by a sensory-cognitive premonitory urge. Complex tics include environmentally dependent social behaviors such as echoing of other people's speech and actions. Recent studies have suggested that adults with TS can show differences to controls in Theory of Mind (ToM): reasoning about mental states (e.g. beliefs, emotions). In this study, twenty-five adults with uncomplicated TS (no co-morbid disorders, moderate tic severity), and twenty-five healthy age and gender matched controls were scanned with fMRI during an established ToM task. Neural activity was contrasted across ToM trials involving reasoning about false-belief, and matched trials requiring judgments about physical states rather than mental states. Contrasting task conditions uncovered differential fMRI activation in TS during ToM involving the right temporo-parietal junction (TPJ), right amygdala and posterior cingulate. Further analysis revealed that activity within the right TPJ as localised by this task covaried with the severity of symptoms including echophenomena, impulse control problems and premonitory urges in TS. Amygdala activation was also linked to premonitory urges, while activity in the left TPJ during ToM was linked to ratings of non-obscene socially inappropriate symptoms. These findings indicate that patients with TS exhibit atypical functional activation within key neural substrates involved in ToM. More generally, our data could highlight an important role for TPJ dysfunction in driving compulsive behaviors.

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OBJECTIVE: Patients with the inherited movement disorder Huntington's disease (HD) exhibit deficits in executive functions and theory of mind (ToM). We investigated these abilities in individuals with the HD gene who were yet to exhibit motor onset. METHOD: Participants were HD gene carriers (n = 20) and healthy controls (n = 26). Gene carriers were prescreened for motor symptoms. Participants completed tasks assessing the understanding of socially inappropriate behaviors, recognition of complex mental states from photographs of peoples' eyes, everyday perspective taking, and executive functions. Gene carriers' task performance was compared to controls', and relationships were explored between ToM, executive functions, and clinical factors including disease burden and mood disorder. RESULTS: Performance was intact on nine of the ten executive measures in premanifest HD, with only a mild deficit in semantic fluency. However, gene carriers exhibited impairments in recognizing faux pas and complex mental states. The Interpersonal Reactivity Index yielded evidence of reduced everyday perspective taking in HD, and differences for empathy and personal distress. Everyday perspective taking was predicted by disease burden and recognition of complex mental states. CONCLUSIONS: We provide evidence that premanifest HD can be associated with changes in ToM. Furthermore, these deficits appear unlikely to result from executive dysfunction. HD gene carriers' impairments highlight the possibility of a relatively selective impact of early neurodegenerative changes in the striatum on ToM. Neuroimaging studies should investigate whether ToM deficits may arise in premanifest HD because of early neuropathology rather than the psychological effects of diagnostic status.

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Huntington's disease (HD) is an inherited neurodegenerative condition. Patients with this movement disorder can exhibit deficits on tasks involving Theory of Mind (ToM): the ability to understand mental states such as beliefs and emotions. We investigated mental state inference in HD in response to ambiguous animations involving geometric shapes, while exploring the impact of symptoms within cognitive, emotional and motor domains. Forty patients with HD and twenty healthy controls described the events in videos showing random movements of two triangles (i.e. floating), simple interactions (e.g. following) and more complex interactions prompting the inference of mental states (e.g. one triangle encouraging the other). Relationships were explored between animation interpretation and measures of executive functioning, alexithymia and motor symptoms. Individuals with HD exhibited alexithymia and a reduced tendency to spontaneously attribute intentions to interacting triangles on the animations task. Attribution of intentions on the animations task correlated with motor symptoms and burden of pathology. Importantly, patients without motor symptoms showed similar ToM deficits despite intact executive functions. Subtle changes in ToM that are unrelated to executive dysfunction could therefore feature in basal ganglia disorders prior to motor onset.

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OBJECTIVE: Huntington's disease (HD) is an inherited movement disorder characterized by choreiform movements and frontostriatal dysfunction. Previous studies have documented executive deficits in HD. We aimed to investigate the effect of cognitive deficits on patients' daily functioning. Furthermore, we sought to explore how independent patients' cognitive difficulties were from their motor and psychiatric symptoms. METHOD: We administered a battery of neuropsychological tasks assessing broader cognitive abilities and executive functions (e.g., verbal fluency, working memory, response inhibition) to 25 patients with HD and 20 healthy controls. Clinical ratings of functional capacity and the severity of motor and psychiatric symptoms were also taken. After establishing that patients with HD demonstrated characteristic cognitive deficits, we explored relationships between performance on neuropsychological tasks and clinical ratings. RESULTS: Patients with HD exhibited deficits on all timed neuropsychological tasks but not on measures of accuracy. Poorer functional capacity was related to cognitive deficits and more severe motor symptoms. Motor and psychiatric symptoms were also related to cognitive performance. Category fluency scores alone predicted 54% of the variance in functional capacity. CONCLUSIONS: Patients with HD exhibited a pattern of cognitive dysfunction that may reflect a generalized slowing in processing. It is important to note that we found that certain cognitive measures may help predict functional capacity in HD. However, we also highlight that performance on neuropsychological tasks can be influenced by motor or psychiatric symptoms. Future studies should consider such confounds when seeking purer measures of cognitive capacity.

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In Huntington's disease (HD), frontostriatal dysfunction may lead to deficits in theory of mind (ToM), in addition to broader cognitive impairment. We investigated relationships between patients' spatial and social perspective taking performance and executive deficits, self-reported everyday perspective taking, motor symptoms, functional capacity and quality of life. Thirty patients with symptomatic HD and twenty-three healthy controls of similar age and education completed two ToM tasks, a scale assessing everyday interpersonal perspective taking, a novel object-based spatial perspective taking task (SPT) and executive measures. Ratings of quality of life, psychiatric symptoms, motor symptom severity and functional capacity were also taken for patients. When compared to controls, patients exhibited significant deficits in ToM and spatial perspective taking and lower everyday perspective taking scores. Executive deficits were linked to poor understanding of socially inappropriate remarks and errors in mental state attribution. This may be the first study to show that aspects of ToM performance are linked to spatial perspective taking, motor symptom severity and functional capacity in HD. Our findings indicate that patients with HD exhibit evidence of reduced perspective taking in everyday life in addition to poor performance on social and SPTs. They also emphasise the need to better specify the precise cognitive and neural bases for ToM deficits in neurodegenerative conditions. Further research exploring the impact of striatal degeneration on perspective taking abilities will make a valuable contribution to the continued development of functional models of frontostriatal circuitry.

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In Tourette syndrome (TS), tics are characteristically preceded by subjective bodily experiences referred to as premonitory sensations. Premonitory sensory phenomena play a key role in behavior therapy for tics, the success of which has also been suggested to be related to inhibitory functioning. We investigated whether TS was associated with altered internal physiological awareness and how this may interact with the neuropsychological characteristics of TS. We compared the awareness of bodily sensations and inhibitory functioning in 18 adult patients with uncomplicated TS and 18 healthy controls. We also explored relationships between these factors, tic severity, and premonitory sensations. Patients with TS exhibited significantly higher scores on the Private Body Consciousness (PBC) scale and inhibitory deficits on traditional and emotional Stroop tests. PBC scores were not correlated with premonitory sensations or tic severity. However, inhibitory functioning was negatively related to PBC scores and premonitory sensations. Relationships between inhibitory performance and tic severity were complex. In conclusion, patients with TS exhibit increased PBC in addition to inhibitory deficits. Aspects of inhibitory functioning are related to PBC, premonitory sensations, and tic severity. Complex interplay between neuropsychological and neurophysiological mechanisms could therefore determine tic severity and the success of behavioral treatments.

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OBJECTIVE: Tourette syndrome (TS) can increase the likelihood of social and emotional difficulties which may shape an individual's personality and self-perception. We investigated personality and affect in patients with TS. METHODS: Twenty-five adults with TS (2 with co-morbid obsessive compulsive disorder, 4 with co-morbid attention-deficit hyperactivity disorder and 4 with both co-morbidities), who were not clinically depressed, and 25 matched controls participated in the study. They completed the Ten-Item Personality Index, the Positive and Negative Affect Scale and the Beck Depression Inventory. RESULTS: Adults with TS exhibited no differences from controls in reported emotional experience or depressive symptoms but did differ for four of the five assessed personality dimensions; extraversion, conscientiousness, openness and emotional stability. Individuals with pure TS (who had no co-morbid conditions) exhibited reduced extraversion and emotional stability compared to controls. Personality scores were not related to tic severity, yet lower emotional stability scores were associated with higher ratings of negative affect. CONCLUSIONS: This study is limited by a restricted sample in terms of size and source. However, our findings indicate that in the absence of depression and common co-morbidities, people with TS differ from controls in indices of personality, which are linked to negative affectivity.

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Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evidence. Many studies have failed to investigate the influence of patient and treatment variables on cognitive functioning. Other difficulties include variation across studies in relation to design, treatment group and assessment tools, poor reporting of methodology and poor specification of the cognitive abilities assessed. Focused and rigorous experimental designs including a range of cognitive measures assessing more precisely defined abilities are needed to fill the gaps in our knowledge and follow up reported patterns in the literature. Longitudinal studies are needed to improve our understanding of the influence of factors such as age, tolerance and the stability of cognitive effects. Future trials comparing the effects of commonly prescribed agents across patient subgroups will offer critical insight into the role of patient characteristics in determining the cognitive impact of particular AEDs.

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TOURETTE SYNDROME (TS) IS A CHRONIC NEURODEVELOPMENTAL DISORDER CHARACTERIZED BY TICS: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients' daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles.

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OBJECTIVE: To investigate theory of mind and the understanding of nonliteral language in patients with Tourette syndrome (TS). BACKGROUND: In TS, striatal dysfunction could affect the functioning of the frontal cortex. Changes in frontal functioning could lead to impairments in theory of mind: the understanding of mental states, such as beliefs, emotions, and intentions. Poor understanding of a speaker's mental state may also impair interpretation of their nonliteral remarks. METHOD: In this study, patients with TS and healthy controls completed tasks to assess their understanding of sarcasm, metaphor, indirect requests, and theory of mind. These tasks were the Pragmatic Story Comprehension Task, the Hinting task, and a faux pas task. Inhibitory ability was also assessed through the use of the Hayling task and a black and white Stroop test. RESULTS: Patients with TS exhibited significant impairment on the faux pas task and Pragmatic Story Comprehension Task despite limited evidence of inhibitory impairment. CONCLUSION: TS may be associated with changes in theory of mind.

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Core symptoms of Tourette's syndrome are assumed to result from inhibitory dysfunction, which could also impair theory of mind. Here the authors report evidence for theory of minddifficulties: patients exhibit deficits in recognizing faux pas and understanding intentionality.

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BACKGROUND: Gilles de la Tourette Syndrome (GTS) is a developmental neuropsychiatric disorder characterised by the presence of chronic motor and phonic tics. Drugs currently used in the treatment of GTS either lack efficacy or are associated with intolerable side effects. There is some anecdotal and experimental evidence that cannabinoids may be effective in treating tics and compulsive behaviour in patients with GTS. There are currently no systematic Cochrane reviews of treatments used in GTS. There is one other Cochrane review being undertaken at present, on the use of fluoxetine for tics in GTS. OBJECTIVES: To evaluate the efficacy and safety of cannabinoids as compared to placebo or other drugs in treating tics, premonitory urges and obsessive compulsive symptoms (OCS), in patients with GTS. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library Issue 4 2008) , MEDLINE (January 1996 to date), EMBASE (January 1974 to date), PsycINFO (January 1887 to date), CINAHL (January 1982 to date), AMED (January 1985 to date), British Nursing Index (January 1994 to date) and DH DATA (January 1994 to date). We also searched the reference lists of located trials and review articles for further information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing any cannabinoid preparation with placebo or other drugs used in the treatment of tics and OCS in patients with GTS. DATA COLLECTION AND ANALYSIS: Two authors abstracted data independently and settled any differences by discussion. MAIN RESULTS: Only two trials were found that met the inclusion criteria. Both compared a cannabinoid, delta-9-Tetrahydrocannabinol (Delta(9)THC), either as monotherapy or as adjuvant therapy, with placebo. One was a double blind, single dose crossover trial and the other was a double blind, parallel group study. A total of 28 different patients were studied. Although both trials reported a positive effect from Delta(9)THC, the improvements in tic frequency and severity were small and were only detected by some of the outcome measures. AUTHORS' CONCLUSIONS: Not enough evidence to support the use of cannabinoids in treating tics and obsessive compulsive behaviour in people with Tourette's syndrome.

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