Rs reflecting their diminished ability 1516647 to recognize and construct objects and orient them in space. These dysfunctions have not yet been addressed in literature on neuropsychological disturbances in PG. In comparison to healthy subjects, pathological gamblers showed substantially worse performance on copying two- and three-dimensional figures, recognizing objects against background noise, and discriminating left from right turns on a map. Methodological similarities between the present study and our prior study of cocaine dependence [31] included enrollment of subjects with addictive disorders and use of a standard copy MedChemExpress 125-65-5 figure task. There were differences in the type of addiction and in the number of tasks performed by subjects. Overall these results provide further support for subtle neurobiological impairment in a behavioral addiction that is not confounded by exogenous chemical use. Our data are also consistent with a substantial body of literature documenting neuropsychological impairments in PG patients [18?0], and they extend prior 
findings by suggesting that the impairments are not restricted to the cognitive domains addressed by neuropsychological testing but also generalize to the sensorimotor domain. Several brain regions influence the drawing of three-dimensional figures, but as evident from research on cortically damaged patients [76] and from neuroimaging work [75,77] the most important of the regions is the parietal cortex. Ventral striatum and related mesolimbic dopaminergic circuitry are traditionally considered to be a key component of reward system involved in addiction [78], and it is commonly hypothesized that HDAC-IN-3 site changes in the mesolimbic pathways underlying motivational processes are responsible for transforming regular 
drives into heightened incentive salience assigned to addiction-related cues [79]. However, recent research suggests a novel factor in the mechanisms underlying incentive sensitization by implicating parietal cortex in the control exerted over striatal signals of salience via integration of visuospatial, motor and cognitive (e.g., hedonic value and categorical boundaries) inputs [80]. In addition to these theoretical considerations, an abundant clinical literature demonstrates parietal cortex changes in the context of chronic addictive behaviors [81,82]. Hence NSSs examination may support theFigure 2. Detection and Recognition of an Object Test (DROT). “High noise” and “low noise” sets were presented separately, with the latter following the former. Subjects were instructed to identify the object embedded in the noise. doi:10.1371/journal.pone.0060885.gNeurological Soft Signs and GamblingTable 1. Demographic and Clinical Characteristics (Means 6 SDs or Ratios) of Study Participants.VariableControl PG (n = 21) (n = 10)T-test (df = 29) tp0.66 0.88 0.86 0.Age (year) Education (year) MMSE (score) Alcohol (drink/week)45.569.9 15.062.8 29.360.9 1.063.43.6614.2 15.161.4 29.461.1 0.661.3 0.060.0 0.060.0.44 20.16 20.19 0.DSM-IV-TR PG criteria met 7.361.2 SOGS 13.563.Fisher’s exact test Gender (M/F) Race (W/B) 13/8 10/11 5/5 7/3 0.74 0.doi:10.1371/journal.pone.0060885.tFigure 3. The Money Road Map Test (RMT). The continuous dotted line represents the path followed by the researcher’s pen. Subjects were asked at each successive turn to indicate whether it was right or left. The smaller dotted line in the lower right serves as a practice trial. doi:10.1371/journal.pone.0060885.gneed to focus on this important r.Rs reflecting their diminished ability 1516647 to recognize and construct objects and orient them in space. These dysfunctions have not yet been addressed in literature on neuropsychological disturbances in PG. In comparison to healthy subjects, pathological gamblers showed substantially worse performance on copying two- and three-dimensional figures, recognizing objects against background noise, and discriminating left from right turns on a map. Methodological similarities between the present study and our prior study of cocaine dependence [31] included enrollment of subjects with addictive disorders and use of a standard copy figure task. There were differences in the type of addiction and in the number of tasks performed by subjects. Overall these results provide further support for subtle neurobiological impairment in a behavioral addiction that is not confounded by exogenous chemical use. Our data are also consistent with a substantial body of literature documenting neuropsychological impairments in PG patients [18?0], and they extend prior findings by suggesting that the impairments are not restricted to the cognitive domains addressed by neuropsychological testing but also generalize to the sensorimotor domain. Several brain regions influence the drawing of three-dimensional figures, but as evident from research on cortically damaged patients [76] and from neuroimaging work [75,77] the most important of the regions is the parietal cortex. Ventral striatum and related mesolimbic dopaminergic circuitry are traditionally considered to be a key component of reward system involved in addiction [78], and it is commonly hypothesized that changes in the mesolimbic pathways underlying motivational processes are responsible for transforming regular drives into heightened incentive salience assigned to addiction-related cues [79]. However, recent research suggests a novel factor in the mechanisms underlying incentive sensitization by implicating parietal cortex in the control exerted over striatal signals of salience via integration of visuospatial, motor and cognitive (e.g., hedonic value and categorical boundaries) inputs [80]. In addition to these theoretical considerations, an abundant clinical literature demonstrates parietal cortex changes in the context of chronic addictive behaviors [81,82]. Hence NSSs examination may support theFigure 2. Detection and Recognition of an Object Test (DROT). “High noise” and “low noise” sets were presented separately, with the latter following the former. Subjects were instructed to identify the object embedded in the noise. doi:10.1371/journal.pone.0060885.gNeurological Soft Signs and GamblingTable 1. Demographic and Clinical Characteristics (Means 6 SDs or Ratios) of Study Participants.VariableControl PG (n = 21) (n = 10)T-test (df = 29) tp0.66 0.88 0.86 0.Age (year) Education (year) MMSE (score) Alcohol (drink/week)45.569.9 15.062.8 29.360.9 1.063.43.6614.2 15.161.4 29.461.1 0.661.3 0.060.0 0.060.0.44 20.16 20.19 0.DSM-IV-TR PG criteria met 7.361.2 SOGS 13.563.Fisher’s exact test Gender (M/F) Race (W/B) 13/8 10/11 5/5 7/3 0.74 0.doi:10.1371/journal.pone.0060885.tFigure 3. The Money Road Map Test (RMT). The continuous dotted line represents the path followed by the researcher’s pen. Subjects were asked at each successive turn to indicate whether it was right or left. The smaller dotted line in the lower right serves as a practice trial. doi:10.1371/journal.pone.0060885.gneed to focus on this important r.
