Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury

Arch Neurol. 2011 Jan;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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Diffuse Axonal Injury / metabolism*
  • Diffuse Axonal Injury / pathology*
  • Diffuse Axonal Injury / physiopathology
  • Female
  • Frontal Lobe / metabolism*
  • Frontal Lobe / pathology
  • Frontal Lobe / physiopathology
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Nerve Net / metabolism*
  • Nerve Net / pathology
  • Nerve Net / physiopathology
  • Young Adult