1: a mental faculty for the proces f ssing of inf formation. 2: a group of mental pr f rocesses th includes attention memory, hat s n, language, learning, reasoning, problem s , solving, an decision making. nd n O OVERVIEW C Cognitive disorders such as Alzheimer’s, schizophrenia, A ADHD, and others take a trem mendous toll on those affecte n ed, their families, and society in general. W While preventative and/or disease-modi ifying therapies r represent the greatest potential impact, effe g ective treatmen nts e c that reduce the devastating cognitive effects would, in the nterim, still pr rovide substan ntial relief to the patients an t nd in s support systems tasked with caring for them. . T The challenge of developing effective pro-cognitive e treatments is amplified by the inherent diff a ficulty in direct tly m measuring cogn nitive processin itself. This limits the ability ng to accurately assess the le evel of a pat tient’s cognitive d dysfunction or any pro-cognitiv changes due to a therapeut a ve e tic in ntervention. T The result? Eith potentially effective drug candidates don her n’t g get identified in the early stage trials, or the cost of a advancing a promising dru p ug through th he later stages b becomes extrem mely time-consu uming and expensive. T The solution to this dilemma would be a sens w sitive and reliab ble p physiological measure of cog m gnitive function that could be p practically applied throughout the drug devel lopment proces ss. PHARM MACOLOGICA TREATMEN AL NTS FOR COG GNITIVE DISOR RDERS Cogniti ive disorders such as Alz zheimer’s, schizophrenia, ADHD, and others, share many com mmon factors relevant to pharma companies en a ndeavoring to treat these diseases: They manifest as d y deficits in vario ous fundamenta cognitive al dom ains, e.g. atten ntion, sensory gating, workin memory, ng etc. The cognitive def ficits proximal to the unde erlying biosses are difficu to measure at the level ult path ological proces ehavior. of be Patie ents with the s same underlyin disease pro ng ocess often pres ent with wide variation in cognitive and behavioral ptoms. symp Ther are no mean re ningful imaging or biochemic markers g cal of t hese diseases which can b used as measures of be nitive impairme ent. cogn Pharm macological T Targets Most e efforts to deve elop treatments for the broad range of s cogniti ve disorders h ave focused on (and will continue to be n d al focused on) modul ating neurona activity through the mechan nisms of ne eurotransmitter regulation, hormonal r activity and/or neuro y, otrophic factors s. These targeted thera apies are intended to regulat neuronal te on mental cognitive processes e functio and normali ze the fundam underly ying the emerg ent behavioral symptoms. F Fortunately, wit the recent technological advancements in th a e electronic senso design, sign processing, and web-based or nal d data manageme ent, that solutio is available now. on n Neuronetrix 1044 E Chestnu ut St Louisville KY 40204 www.neuronet trix.com 502‐5 561‐9040

Standardized psychometric/psychological testing can provide useful measures at the level of behavior, and are generally required as pivotal endpoints in late stage trials. However, these tests often lack the sensitivity, reliability, and repeatability required for studies involving a reasonable number of subjects and which can be completed in an economically viable timeframe. These efforts have resulted in several therapies which have proven to be moderately effective for many patients: Cholinesterase inhibitors and glutamate regulators for Alzheimer’s disease. Dopaminergic and serotonergic receptor...

E EEGs recording provide un gs nique advantages for use in e evaluating cogn nitive disorders: A primary ph hysiologic meas sure of the syn nchronous, larg gescale synaptic activity under c rlying all brain functions. f Have millisec cond resolution and can thereby capture many rapidly occurring aspects of regulatory sensory, an y, nd cognitive processing. Can be mod dulated due to the effects of psychotrop o pic compounds and/or in response to various external stimul a li. Can be recor rded while the brain is in a resting state or e while perform ming specific co ognitive tasks. Q Quantitative...

C COGNISION Overcom the Limit N™ mes tations of P Previous Met thods T The COGNISION™ System fr rom Neuronetrix was designed f from the outse to overcome the limitatio et ons of researc cho oriented methods and equipm ment and deliver on the promise o advanced neu of uro-electrophys siological techn niques. OGNISION™ Sy ystem includes an advanced predictive s The CO analytic classification system called reCOGNISIO c n ON™ which learns to classify subj ject data based upon user-def d fined metamodels s. Unique advantages of reCOGNISION™ e f ™: Any neuro-related d sification. class Allow the user...