NeuroTrax Science Team and Glen M. Doniger, PhD

As the global population ages, there is an urgent need to identify individuals at risk for cognitive decline before the emergence of significant symptoms. Traditional cognitive screening provides valuable information, but combining objective cognitive metrics with measures of brain physiology offers a more complete view of brain health. A 2026 study by Zifman and colleagues demonstrates this potential by pairing NeuroTrax digital cognitive neurometrics with combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate the relationship between brain connectivity and cognitive risk in older adults (1).

The study evaluated 454 community-dwelling older adults with a mean age of 61.4 years. Researchers focused on interhemispheric connectivity (IHC) within the dorsolateral prefrontal cortex (DLPFC), a brain region involved in executive control and working memory. Using the non-invasive Delphi-MD TMS-EEG system, researchers magnetically stimulated one side of the prefrontal cortex and recorded the millisecond-level electrical response traveling across the brain’s hemispheres.

Participants also completed a comprehensive cognitive evaluation that included NeuroTrax digital neurometrics. Based on the cognitive scores, researchers applied K-means clustering to classify participants into cognitively normal and cognitively impaired groups and examined brain connectivity in these groups.

The results revealed a strong relationship between DLPFC connectivity and cognitive status. Participants classified as cognitively impaired had significantly lower interhemispheric connectivity than cognitively normal participants. A single-unit decrease in right DLPFC connectivity was associated with 4.35-fold higher odds of cognitive impairment, while a unit decrease in left DLPFC connectivity was associated with 3.03-fold higher odds. These relationships remained significant after adjusting for age and sex.

The link between objective cognitive metrics and underlying brain physiology is supported by prior research with NeuroTrax. Sasson and colleagues used diffusion tensor imaging (DTI) to examine white matter integrity in normal aging, demonstrating associations between specific cognitive domains and the microstructural integrity of corresponding white matter pathways. Executive function, for example, was associated with integrity of the superior longitudinal fasciculus (2). While structural imaging provides data on brain anatomy, longitudinal cognitive assessment tracks how function changes over time. In research on brain plasticity, Lampit and colleagues paired NeuroTrax with functional MRI in healthy older adults engaged in computerized cognitive training. The study identified functional and structural brain changes associated with training, with these changes relating to improvements in NeuroTrax global cognition (3). Together, these findings illustrate the power of combining objective cognitive testing with physiologic measures, albeit impractical for routine clinical use.

Enter the 2026 Zifman study, which demonstrates a practical approach for integrating digital cognitive neurometrics with sophisticated brain network measurements. Indeed, pairing NeuroTrax with technologies like in-clinic TMS-EEG offers an unprecedented opportunity to examine how brain function translates into measurable cognitive performance. Rather than relying on a single measure, this multimodal approach offers a more complete picture of cognitive aging. The Zifman study represents a compelling example of this direction, demonstrating that reduced prefrontal interhemispheric connectivity is strongly associated with cognitive impairment as defined by objective neurometrics.

With advances in technologies for early identification and longitudinal monitoring of cognitive decline, integrating clinically viable measures of brain physiology with NeuroTrax testing bridges the gap between advanced neuroscience and cognitive assessment. By linking measurable cognitive performance with the neuroanatomy and networks supporting it, researchers and clinicians can better understand how the aging brain changes over time, bringing brain science into their routine work.

References

[1] Zifman, N., Fogel, H., Rosenberg, R., Levy-Lamdan, O., Verhovski, N., Strauss, T., Bischof, E., and Goshen, A. (2026) Interhemispheric connectivity measured with transcranial magnetic stimulation and EEG as an objective marker of cognitive risk. Brain Communications, 8(4):fcag251. DOI: 10.1093/braincomms/fcag251

[2] Sasson, E., Doniger, G.M., Pasternak, O., Tarrasch, R., and Assaf, Y. (2012). Structural correlates of cognitive domains in normal aging with diffusion tensor imaging. Brain Structure and Function, 217(2), 503–515. DOI: 10.1007/s00429-011-0344-7

[3] Lampit, A., Hallock, H., Suo, C., Naismith, S.L., and Valenzuela, M. (2015). Cognitive training-induced short-term functional and long-term structural plastic change is related to gains in global cognition in healthy older adults: A pilot study. Frontiers in Aging Neuroscience, 7:14. DOI: 10.3389/fnagi.2015.00014

NeuroTrax Science Team and Glen M. Doniger, PhD

Parkinson's disease (PD) is known primarily as a movement disorder, but cognitive decline is a core component of the disease that can detrimentally affect quality of life. Subtle impairments in executive function, attention, and cognitive flexibility may emerge early, sometimes before they become apparent on routine clinical assessment. NeuroTrax provides an objective, validated method for measuring these changes, allowing clinicians to better understand the relationship between cognition and mobility while monitoring disease progression and treatment response (1,2).

A key finding in PD research is that walking is not simply an automatic motor function. Studies by Hausdorff and colleagues demonstrated that mobility requires continuous executive control and attention, particularly during complex activities like walking while performing another task or negotiating obstacles [1,3]. These findings highlight the important role that cognition, particularly executive function and attention, plays in maintaining safe and effective mobility in Parkinson’s disease. Indeed NeuroTrax testing identified a signature cognitive profile in Parkinson's disease characterized by impaired executive function and attention, with memory and processing speed relatively intact in earlier disease stages (3).

NeuroTrax-based studies have consistently demonstrated that digital cognitive assessment effectively captures the frontostriatal dysfunction associated with PD, supporting its use as a valuable complement to traditional neurological examination (2). Cognitive symptoms are often incipient, emerging slowly over time, and objective digital assessment is well-suited to detect subtle changes that would otherwise go unnoticed, enabling earlier intervention and more personalized patient management.

Beyond general profiling of cognitive function in PD, NeuroTrax testing has contributed to a better understanding of disease subtypes. Studies have shown that patients with the postural instability and gait difficulty (PIGD) subtype experience more rapid decline in executive function than those with tremor-dominant disease (4). Additionally, imaging studies have demonstrated that gray matter atrophy in cortical and subcortical regions is associated with freezing of gait, one of the most disabling motor symptoms associated with PD (5).

A recent study by Peterson and colleagues examined the relationship between actual and perceived balance ability. Findings indicated that underestimating or overestimating balance ability was related to poorer global cognition and executive function, and underestimating balance was linked to poorer mobility-related quality of life (6). Thus combining objective cognitive testing with measures of physical function may reveal symptoms difficult to identify by observation and help clinicians better tailor rehabilitation strategies.

Objective measurement helps validate symptoms that patients describe but are difficult to quantify, including "brain fog," fear of falling, or reduced confidence during everyday activities. Work by Costello and colleagues has demonstrated a relationship between cognitive impairment and employment status in people with PD, highlighting the pervasive impact cognitive changes can have on daily life (7).

NeuroTrax has also been extensively used to evaluate the effectiveness of advanced PD interventions. Studies have explored its role in supporting candidate selection and monitoring outcomes following deep brain stimulation (DBS); research has also documented improved cognitive and motor performance following non-invasive brain stimulation, including deep repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) (8-10). Other studies have shown improvement following pharmacological therapies (e.g., methylphenidate) and structured computerized cognitive remediation programs, underscoring the utility of objective cognitive assessment in the longitudinal tracking of treatment response (11,12).

As PD management evolves, objective cognitive assessment is becoming an increasingly important part of comprehensive care. NeuroTrax provides clinicians with precise, repeatable measurements that complement traditional motor evaluations while helping patients better understand their cognitive health. By objectively tracking cognitive function alongside mobility, NeuroTrax supports earlier identification of cognitive decline, more personalized rehabilitation strategies, and more informed monitoring of treatment efficacy throughout the PD disease course.

References

[1] Yogev, G., Giladi, N., Peretz, C., Springer, S., Simon, E.S., and Hausdorff, J.M. (2005). Dual tasking, gait rhythmicity, and Parkinson’s disease: Which aspects of gait are attention demanding? European Journal of Neuroscience, 22(5), 1248–1256. DOI: 10.1111/j.1460-9568.2005.04298.x

[2] Doniger, G.M., Simon E.S., Okun, M.S., Rodriguez, R.L., Jacobson, C.E., Weiss, D., Rosado, C., and Fernandez, H.H. (2006). Construct validity of a computerized neuropsychological assessment in patients with movement disorders. Movement Disorders, 21(S15), S656-S657. DOI: 10.1002/mds.21249

[3] Hausdorff, J.M., Doniger, G.M., Springer, S., Yogev, G., Giladi, N., and Simon, E.S. (2006). A common cognitive profile in elderly fallers and in patients with Parkinson’s disease: The prominence of impaired executive function and attention. Experimental Aging Research, 32(4), 411–429. DOI: 10.1080/03610730600875817

[4] Rosenberg-Katz, K., Herman, T., Jacob, Y., Giladi, N., Hendler, T., and Hausdorff, J.M. (2013). Gray matter atrophy distinguishes between Parkinson disease motor subtypes. Neurology, 80(16), 1476–1484. DOI: 10.1212/WNL.0b013e31828cfaa4

[5] Herman, T., Rosenberg-Katz, K., Jacob, Y., Giladi, N., and Hausdorff, J.M. (2014). Gray matter atrophy and freezing of gait in Parkinson’s disease: Is the evidence black-on-white? Movement Disorders, 29(1), 134–139. DOI: 10.1002/mds.25697

[6] Peterson, D.S., Longhurst, J.K., Albrecht, F., Weller, J., Vasquez, J., Zarif, M., Gudesblatt, M., and Hooyman, A. (2026). Discordance between actual and perceived balance ability relates to quality of life and global cognition in a clinical sample of Parkinson patients. Journal of Parkinson’s Disease, 16(3), 529–538. DOI: 10.1177/1877718X261423310

[7] Costello, S., Marino, J., Fang, A., Khan, A., Reilly, K., Weller, J., Jo, M., Vasquez, J., Zarif, M., and Gudesblatt, M. (2025). Parkinson’s disease, cognition and employment: Analysis of cognition function in people with Parkinson’s disease who remain employed and those who self-report as unemployed. Neurology, 104(7_S1), 5134. DOI: 10.1212/WNL.0000000000212159

[8] Oyama, G, Rodriguez, R.L., Jones, J.D., Swartz, C., Merritt, S., Unger, R., Hubmann, M., Delgado, A., Simon, E., Doniger, G.M., Bowers, D., Foote, K.D., Fernandez, H.H., and Okun, M.S. (2012). Selection of deep brain stimulation candidates in private neurology practices: Referral may be simpler than a computerized triage system. Neuromodulation, 15(3), 246–250. DOI: 10.1111/j.1525-1403.2012.00437.x

[9] Seri-Fainshtat, E., Israel, Z., Weiss, A., and Hausdorff, J.M. (2013). Impact of sub-thalamic nucleus deep brain stimulation on dual tasking gait in Parkinson’s disease. Journal of Neuroengineering and Rehabilitation, 10:38. DOI: 10.1186/1743-0003-10-38

[10] Dagan, M., Herman, T., Mirelman, A., Giladi, N., and Hausdorff, J.M. (2017). The role of prefrontal cortex in freezing of gait in Parkinson’s disease: Insights from a deep repetitive transcranial magnetic stimulation exploratory study. Experimental Brain Research, 235(8), 2463–2472. DOI: 10.1007/s00221-017-4981-9

[11] Auriel, E., Hausdorff, J.M., Herman, T., Simon, E.S., and Giladi, N. (2006). Effects of methylphenidate on cognitive function and gait in patients with Parkinson’s disease: A pilot study. Clinical Neuropharmacology, 29(1), 15–17. DOI: 10.1097/00002826-200601000-00005

[12] Milman, U., Atias, H., Weiss, A., Mirelman, A., and Hausdorff, J.M. (2014). Can cognitive remediation improve mobility in patients with Parkinson’s disease? Findings from a 12 week pilot study. Journal of Parkinson’s Disease, 4(1), 37–44. DOI: 10.3233/JPD-130321