Neurological Soft Signs in Individuals with Pathological Gambling

Citation: Elman I, Gurvits TV, Tschibelu E, Spring JD, Lasko NB, et al. ( Neurological Soft Signs in Individuals with Pathological Gambling Igor Elman 0 Tamara V. Gurvits 0 Evelyne Tschibelu 0 Justin D. Spring 0 Natasha B. Lasko 0 Roger K. Pitman 0 Antonio Verdejo Garca, University of Granada, Spain 0 1 Providence VA Medical Center, Harvard Medical School , Cambridge, Massachusetts , United States of America, 2 Cambridge Health Alliance, Harvard Medical School , Cambridge, Massachusetts , United States of America, 3 Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts , United States of America Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response. - Funding: This work was supported by grant DA #017959 (to IE) from the National Institute on Drug Abuse. This study was also supported with resources and the use of facilities at the Providence VA Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Parallel to the ongoing expansion of legalized gambling activities is an increase in the prevalence of pathological gambling (PG) [1,2]. Pathological gambling afflicts up to 5% of the general adult population and it costs American society an estimated $54 billion annually due to crime, decreased productivity, and bankruptcies [37]. These estimates are likely conservative, given that PG is not a conspicuous addiction, and it is devoid of typical symptoms of intoxication, needle marks, or overdose. It may only become noticeable in later stages of the illness, with the emergence of highly visible behaviors including attempted suicide in up to 24% of untreated individuals [79]. To improve prevention and treatment of PG, it is important to identify its behavioral markers and their neural correlates. A relatively consistent finding in functional brain imaging studies of PG is failure of prefrontal cortical areas to activate when challenged by cognitive tasks that normally evoke cerebral blood flow and metabolic responses in these regions [1017]. Likewise, neuropsychological impairments are commonly documented in PG patients [1820], but their role in the course of the disorder remains unclear [16], as they do not reliably reflect the severity of gambling problems [21,22]. The nonspecificity of PG neuropsychological findings may be partially attributable to the multidimensionality of the tests employed [23]. Additionally, some results may reflect poor motivation and attention [24,25] rather than PGrelated primary neuropathology, which has not yet been well defined [23]. Neurological assessment paradigms may be of value in revealing cortical abnormalities in PG. In this regard, neurological soft signs (NSSs) are reliable [2628], easily administered and temporally stable [29,30] markers of neurological compromise, which impose fewer cognitive demands than neuropsychological tests and are therefore less influenced by performance confounds [31]. In contrast to hard neurological signs localizable to a specific brain site, their soft counterparts are attributed to wider brain regions and functionally connected neuroanatomical systems, involved in integrative neurological functions such as sensory perception, coordination and motor sequencing [32,33]. Neurological soft signs have been observed in a growing number of neuropsychiatric syndromes including mood disorders [3436], obsessive-compulsive disorder (OCD) [3739], post-traumatic stress disorder [26,27], impulse control disorder [40], schizophrenia [32,34,41], and attention deficit hyperactivity disorder [42]. Furthermore, an inverse relationship between NSSs scores and total brain volume has been noted in psychopathological populations [27,43] adding support to the generalized rather than localized NSSs nature. In a previous paper, we reported that cocaine dependence is characterized by the NSS of constructional apraxia [31]. As with PG, cocaine dependence is classified in the DSM-V draft among Substance Use and Addictive Disorders [44]. However, in addition to its representing a behavioral addiction, a substance addiction to cocaine exerts profound chemical effects on the brain that may even result in such injuries as subarachnoid/parenchymal hemorrhages [4556] and infarcts [47,50]. Because it is not confounded by exogenous neurotoxicity, PG offers a unique opportunity to test whether a purely behavioral addiction is accompanied by neurological compromise. To our knowledge, NSSs have not yet been investigated in pathological gamblers. The presence in PG of obsessive/compulsive and impulsive features each of which has been previously linked with NSSs [40,57,58] suggests that NSSs may also be seen in PG. Accordingly, in this project we assessed three NSSs in PG and healthy subjects. These were: a) copying two- and threedimensional figures (as previously tested in cocaine subjects [31]); b) filtration of visual signal from noise; and c) left-right orientation in the form of reading and understanding a simple road map. These visuospatial and sensory integration tasks were selected for the present project from our comprehensive NSSs assessment battery based upon their discriminative ability in drugdependent and other psychiatric patients [27,31,59] as well as their ease of administration as paper-and-pencil tasks. We hypothesized that patients with PG would be more impaired than healthy subjects on all three tasks. Subjects Twenty-one subjects who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM IV-TR) criteria for PG, and 10 non-gamblers who did not meet DSM IV-TR criteria for any disorder, were recruited by newspaper advertisement for participation in a previous study on the neurobiology of PG. The biochemical [60] and psychosocial [61] stress responsivity findings from that study have been reported elsewhere. After a full explanation of the procedures, all subjects gave written informed consent to the McLean Hospital Institutional Review Board-approved protocol. Those with any (...truncated)