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Original Contribution
January 2011

Deficits in Functional Connectivity of Hippocampal and Frontal Lobe Circuits After Traumatic Axonal Injury

Author Affiliations

Author Affiliations: Center for Brain Health, University of Texas at Dallas, Richardson (Dr Marquez de la Plata); and the Departments of Psychiatry (Dr Marquez de la Plata, Messrs Shokri Kojori and Grinnan, and Ms Krishnan), Neurology (Dr Diaz-Arrastia, Mss Garces and Moore, and Mr Pidikiti), Clinical Sciences (Dr Spence), Radiology (Neuroradiology) (Drs Devous and McColl), and Neurological Surgery (Dr Madden), University of Texas Southwestern Medical Center, Dallas.

Arch Neurol. 2011;68(1):74-84. doi:10.1001/archneurol.2010.342

Objective  To examine the functional connectivity of hippocampal and selected frontal lobe circuits in patients with traumatic axonal injury (TAI).

Design  Observational study.

Setting  An inpatient traumatic brain injury unit. Imaging and neurocognitive assessments were conducted in an outpatient research facility.

Participants  Twenty-five consecutive patients with brain injuries consistent with TAI and acute subcortical white matter abnormalities were studied as well as 16 healthy volunteers of similar age and sex.

Interventions  Echo-planar and high-resolution T1-weighted images were acquired using 3-T scanners. Regions of interest (ROI) were drawn bilaterally for the hippocampus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex and were used to extract time series data. Blood oxygenation level–dependent data from each ROI were used as reference functions for correlating with all other brain voxels. Interhemispheric functional connectivity was assessed for each participant by correlating homologous regions using a Pearson correlation coefficient. Patient functional and neurocognitive outcomes were assessed approximately 6 months after injury.

Main Outcome Measures  Interhemispheric functional connectivity, spatial patterns of functional connectivity, and associations of connectivity measures with functional and neurocognitive outcomes.

Results  Patients showed significantly lower interhemispheric functional connectivity for the hippocampus and ACC. Controls demonstrated stronger and more focused functional connectivity for the hippocampi and ACC, and a more focused recruitment of the default mode network for the dorsolateral prefrontal cortex ROI. The interhemispheric functional connectivity for the hippocampus was correlated with delayed recall of verbal information.

Conclusions  Traumatic axonal injury may affect interhemispheric neural activity, as patients with TAI show disrupted interhemispheric functional connectivity. More careful investigation of interhemispheric connectivity is warranted, as it demonstrated a modest association with outcome in chronic TBI.