A multimodal neuroimaging study of brain abnormalities and clinical correlates in post treatment Lyme disease

Abstract

Lyme disease is the most common vector-borne infectious disease in the United States. Post-treatment Lyme disease (PTLD) is a condition affecting 10–20% of patients in which symptoms persist despite antibiotic treatment. Cognitive complaints are common among those with PTLD, suggesting that brain changes are associated with the course of the illness. However, there has been a paucity of evidence to explain the cognitive difficulties expressed by patients with PTLD. This study administered a working memory task to a carefully screened group of 12 patients with well-characterized PTLD and 18 healthy controls while undergoing functional MRI (fMRI). A subset of 12 controls and all 12 PTLD participants also received diffusion tensor imaging (DTI) to measure white matter integrity. Clinical variables were also assessed and correlated with these multimodal MRI findings. On the working memory task, the patients with PTLD responded more slowly, but no less accurately, than did controls. FMRI activations were observed in expected regions by the controls, and to a lesser extent, by the PTLD participants. The PTLD group also hypoactivated several regions relevant to the task. Conversely, novel regions were activated by the PTLD group that were not observed in controls, suggesting a compensatory mechanism. Notably, three activations were located in white matter of the frontal lobe. DTI measures applied to these three regions of interest revealed that higher axial diffusivity correlated with fewer cognitive and neurological symptoms. Whole-brain DTI analyses revealed several frontal lobe regions in which higher axial diffusivity in the patients with PTLD correlated with longer duration of illness. Together, these results show that the brain is altered by PTLD, involving changes to white matter within the frontal lobe. Higher axial diffusivity may reflect white matter repair and healing over time, rather than pathology, and cognition appears to be dynamically affected throughout this repair process.

An fMRI analysis of verbal and non-verbal working memory in people with a past history of opioid dependence

“…Positive contrast values indicated higher BOLD signal during the verbal or non-verbal WM task compared to the control task (see Table 4 and Figure 4 ). The results of the verbal WM task in both groups generally agreed with previous findings that included activation with the cerebro-cerebellar circuit and secondary motor regions ( Chen and Desmond, 2005 ; Marvel and Desmond, 2012 ; Marvel et al, 2012 , 2022 ). Both groups revealed activity in the prefrontal cortex and superior cerebellum.…”

“…Structural scans were co-registered to the mean image, normalized to the Montreal Neurological Institute (MNI) stereotaxic space, and underwent spatial smoothing (FWHM = 8 mm). Individual hemodynamic response functions (HRFs) were obtained using an event-related finger tapping paradigm that was collected during the same fMRI session to create regressors derived from the peak activation voxel within the left primary motor cortex, following Chen and Desmond (2005) , Desmond et al (1997) , Marvel and Desmond (2012) , and Marvel et al (2022) . Individual HRFs were obtained instead of using canonical HRFs in the analyses to control for potential individual (or clinical group) HRF differences ( Ances et al, 2011 ; Kim and Ogawa, 2012 ) and had been processed previously using SPM8.…”

“…Within a run, trials were jittered with an inter-trial interval (ITI) that lasted 6-9 s. A trial was initiated at the end of the ITI rather than triggered by user response. Ten trials (25%) per run did not include any probe at all so that the hemodynamic response measured during the maintenance phase could be visualized more clearly, without interference from the button press of the retrieval phase, as done in previous studies (Marvel and Desmond, 2012;Marvel et al, 2012Marvel et al, , 2022. In the no-probe trials, participants viewed a blank screen throughout the retrieval phase, and no response was expected.…”

“…Clusters are listed by decreasing t-score of the peak voxel within a cluster. Bolded regions of interest reflect consistency with previous WM imaging studies (Pollmann and Von Cramon, 2000;Chen and Desmond, 2005;Champod and Petrides, 2007;Marvel and Desmond, 2012;Marvel et al, 2012Marvel et al, , 2019Marvel et al, , 2022Liao et al, 2014;Sobczak-Edmans et al, 2016). Coordinates are listed according to the Montreal Neurological Institute (MNI) atlas within SPM12.…”

Superior Efficacy of Combination Antibiotic Therapy versus Monotherapy in a Mouse Model of Lyme Disease

“…However, treatment delays significantly affect antibiotic efficacy, and many patients experience chronic musculoskeletal pain, fatigue, and cognitive dysfunction (5)(6)(7)(8). Studies on patients with PTLD show not only that immune activation/inflammation lingers in the brain, but also that dynamic changes in the frontal lobe associated with slower processing speeds occur (9,10). Treatment for PTLD is mired by a lack of tests for persistent infection and mixed results on treating chronic Lyme disease in clinical trials (11)(12)(13)(14).…”