Participants

Men and women with a diagnosis of nonpsychotic MDD were recruited from a university counseling and psychiatric services clinic. Participants in the MDD group were included if they met diagnostic (DSM-IV-TR) criteria for current MDD,33 confirmed by the Mini International Neuropsychiatric Interview (MINI34). The MINI is an appropriate tool for assigning threshold-level psychiatric diagnoses in research settings and has strong diagnostic agreement with other clinical interviews such as the Structured Clinical Interview for the DSM.35 Exclusion criteria included bipolar or psychotic disorders, self-injurious or suicidal behavior, or a history of neurological disorders or head injuries resulting in a loss of consciousness. Healthy comparison participants who did not meet criteria for MDD via the MINI were also recruited and included if they reported no previous or current history of neuropsychiatric disorders, neurological disorders or head injuries. In addition, handedness (Edinburgh Handedness Inventory) was assessed to minimize heterogeneity in neurocognitive measures, but was not used as an exclusionary factor. All eligible individuals were invited to visit the laboratory for a clinical interview and neurophysiological testing at baseline before beginning the MAP training intervention. Sixty-nine participants (33 depressed, 36 nondepressed) who met the inclusion criteria were initially enrolled in the study,30 and 22 depressed and 30 nondepressed individuals completed the 8-week MAP training intervention with complete baseline and post-intervention data (~75% retention rate). No significant differences were observed in the demographic, behavioral or cognitive status between those who finished the MAP intervention and those who did not. Before participation in this study, participants provided written informed consent that was approved by the Institutional Review Board at Rutgers, The State University of New Jersey.

Recruited participants were scheduled for study entry and baseline assessments by trained clinical research staff. Potential participants were given contact information, including a phone number and email address for the study staff/coordinator, who provided study information and scheduled an initial screening to determine eligibility. After determining initial eligibility, the study coordinator scheduled a secondary screening appointment for the informed consent process and baseline assessments, during which they completed a structured diagnostic interview, neurocognitive assessment and a maximal aerobic fitness test (VO 2 peak). Subsequently, participants were assigned to the 8-week MAP training intervention. At the end of the 8-week program, all the participants were invited back to the laboratory to complete the same battery of assessments, including measures of clinical symptoms, neurocognitive function and aerobic fitness (VO 2 peak) following the same protocol.

MAP training intervention

MAP training is a neurobehavioral intervention developed from basic neuroscientific studies suggesting that MAP training may work synergistically to improve cognitive and brain health.17, 36 For the mental component, participants engaged in FA meditation, which is challenging to learn and practice.37, 38 During FA meditation, participants sat in silence in a cross-legged or otherwise comfortable upright posture. For the meditation practice, participants were instructed to bring their full focus of attention to the breath and to count each breath if that helped to maintain focus on the breath. If their attention drifted to thoughts about the past or future, participants were instructed to acknowledge this change and return their attention to the breath. With practice, one recognizes the transient nature of thoughts and learns to monitor and accept moment-to-moment changes in attention.39 After 20 min of sitting meditation, participants engaged in 10 min of slow-walking meditation, this time focusing their attention on their feet as they transitioned from one foot to the other in a slow walk with other participants. The 10 min walking portion of the meditation session was not only a secondary form of FA meditation training, but also a chance to return blood flow to the extremities before the upcoming session of aerobic exercise. Immediately following the meditation session, participants prepared for the exercise component.

For the physical component, participants performed aerobic exercise at a moderate intensity for 30 min. Following a 5-min warm-up, participants exercised either on a treadmill or cycle ergometer at a heart rate (HR) intensity range corresponding to 50–70% VO 2 peak as determined by their individual baseline fitness assessment before MAP training. Trained research staff supervised all exercise sessions and monitored intensity by assessing HR throughout exercise. This dose of exercise (that is, intensity and duration) is consistent with public health recommendations and is known to reduce depressive symptoms among individuals with MDD.40, 41 After 30 min of aerobic exercise, participants cooled down for ~5 min.

MDD diagnosis and assessment of depression symptom severity

At baseline, the Mini Neuropsychiatric Diagnostic Interview (MINI; manic/hypomanic episodes, obsessive-compulsive disorder, substance and alcohol use disorders) was used to confirm clinical diagnosis of MDD. The MINI is a brief structured interview that has been used extensively to aid in making diagnoses of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and International Classification of Diseases-10 (ICD-10) psychiatric disorders. The reliability and validity of this instrument has been previously established.34, 42, 43

Depressive symptoms

The Beck Depression Inventory-II (BDI-II44) is a 21-item, self-report inventory of the severity of current depressive symptoms. The BDI was used to assess the severity of depressive symptoms at baseline and at post-intervention. Higher total scores reflect greater subjectively perceived depressive symptomatology. The BDI-II in this sample demonstrated good internal consistency (α=0.92) at baseline and the point biserial correlation coefficient of MDD diagnosis with BDI-II scores was 0.80, P<0.01.

Ruminative thought patterns

Participants completed the Ruminative Responses Scale (RRS45) before and after MAP training. The RRS includes 22 items describing thoughts and responses that are focused on the self, the symptoms and the potential consequences and causes of their depressed mood. In addition, the scale is further defined by three subscales, which include depression, brooding and reflection.46 Participants were asked to indicate how often they exhibit a certain behavior on a scale from 1 (almost never) to 4 (almost always) when they feel down, sad or depressed. The RRS scale demonstrated appropriate internal consistency (α=0.93).

Cardiorespiratory fitness and physical activity assessment

Cardiorespiratory fitness (VO 2 peak) was assessed by a maximal oxygen consumption test using a motor-driven treadmill and a modified Bruce protocol.47 During this test, participants began walking on a treadmill, which increased in speed and incline every 2 min until volitional exhaustion or VO 2 peak criteria were met. A Polar HR monitor (Polar Electro, Kempele, Finland) was used to measure HR throughout the test, and a rating of perceived exertion48 was taken 1 min into each stage. Rating of perceived exertion allows participants to rate their perceived physical effort on a numerical scale ranging from 6 to 20, which correlates with HR during exercise.49 Relative VO 2 peak (ml kg−1 min−1) was determined from direct expired gas exchange data from an indirect calorimetry metabolic system and was established as the maximal average oxygen consumption when at least three of the following criteria were met: (1) a plateau in VO 2 values despite a progressive increase in workload, (2) a maximal HR within 10 beats per minute (b.p.m.) of age-predicted maximal values (220 b.p.m. minus age in years), (3) a respiratory exchange ratio greater than 1.10 or (4) a rating of perceived exertion greater than or equal to 17. Oxygen consumption was measured through indirect calorimetry using a ParvoMedics True Max 2400 Metabolic Measurement Cart (ParvoMedics, Sandy, UT, USA) and was averaged over 15-s intervals. A 3–5 min cool-down was then performed at 2.5 m.p.h. and 0% grade to ensure participants returned to near baseline cardiovascular values. HR was recorded during the fitness assessment and was used to define individual training zones during the intervention. Fitness was reassessed upon completion of the 8-week intervention using the same procedures.

In addition, participants were also asked to recall the amount of physical activity that they engaged in at baseline and following MAP training using the International Physical Activity Questionnaire.50 The International Physical Activity Questionnaire-short-form assesses the frequency and duration of moderate and vigorous intensity activity and walking physical activity. These data were summarized to report physical activity by weighting the energy expenditure for these categories of activity to produce MET-minutes of physical activity.

Cognitive control

A modified arrow version of the Eriksen flanker task30, 51 was presented using E-Prime version 2.0 software (Psychology Software Tools, Pittsburgh, PA, USA). Participants completed the flanker task at baseline and post-intervention to assess changes in behavioral and neurophysiological cognitive control processes. The flanker task is composed of two conditions, congruent and incongruent, during which participants are asked to press either a left or right button corresponding to the direction of a centrally located target arrow. The congruent trials consisted of the central target being flanked by arrows pointing in the same direction (for example, ««<), while incongruent trials involved the target being flanked by arrows pointing in the opposing direction (for example, «>«). A set of instructions preceded the first trial that explained which button press would be used to indicate the direction of the central or target arrow. Participants performed a button press with their left thumb when the target arrow pointed to the left (<) and a button press with their right thumb when the target arrow pointed to the right (>). In addition, participants were instructed to respond as quickly and accurately as possible for each trial. Each trial began with a black fixation cross (+) in the center of a white screen for 500 ms, followed by 1.5 cm tall × 8 cm long black arrows centered focally on a white background for 100 ms with a response window of 1500 ms. A random inter-stimulus time interval of 1100, 1300, or 1500 ms was used between each visual fixation (+) and the stimulus in order to reduce potential anticipatory responses. Following the instructions, participants completed 20 practice trials, including equiprobable congruent and incongruent trials. Performance feedback was provided and any remaining questions were resolved during the practice trials to ensure a sufficient familiarization and understanding of the task. After the practice, the participants completed two blocks of 110 trials with equiprobable congruency and directionality of the stimuli. The stimuli were presented on a monitor at a distance of 70 cm centered to the nasion and the vertical and horizontal visual angles were 1.2° and 6.6°, respectively. In addition to behavioral measures of accuracy and reaction time, continuous electroencephalographic data were collected during the flanker task to derive N2 and P3 component amplitudes.

Event-related potentials

Continuous electroencephalographic activity was recorded from 64 scalp sites using a HydroCel Geodesic Sensor Net and Electrical Geodesics (Eugene, OR, USA) amplifier system (20 K nominal gain, bandpass=0.1–100 Hz) and arranged according to the International 10-10 system.52 The electro-oculogram was recorded from electrodes placed above and below each eye. Continuous data were initially referenced to the vertex electrode (Cz) and digitized continuously at 250 Hz with a 24-bit analog-to-digital converter. Impedances were maintained below 50 kΩ. Although lower impedances are typically recommended, previous research has produced acceptable electroencephalographic signals when data were collected with higher scalp impedances,53 and similar values have been used in previous studies of cognitive control and depression.54, 55

Following collection, data were re-referenced to the average of the left and right mastoids56, 57 and bandpass filtered with a low-pass frequency of 30 Hz and high-pass frequency of 0.1 Hz. The continuous electroencephalographic data were manually inspected and periods with large movement-related artifacts (eye blinks, eye movement and muscle activity) were removed using NetStation 4.0 (Electrical Geodesic). Stimulus-locked epochs were created from 100 ms pre-stimulus to 1000 ms post stimulus and baseline-adjusted using the 100 ms pre-stimulus period. NetStation detection software, which allows for the adjustment of settings for detecting and marking artifacts and contaminated segments, was used to detect eye blinks, vertical and horizontal eye movements, and bad channels. Marked segments were visually inspected and rejected if they contained (1) eye movements exceeding 55 μV, (2) eye blinks exceeding 14 μV or (3) greater than or equal to 10 bad channels exceeding 200 μV. In each case, a moving average of 20 samples combined with threshold values was used. Using spherical spline interpolation, bad channels were then replaced from the remaining channels in ‘good’ segments. Trials were also visually inspected for remaining artifacts, and data from individual channels containing artifacts were rejected on a trial-by-trial basis. Only correct trials were used for the corresponding ERP analyses. Using a mean amplitude approach,58 the N2 component was defined as the mean amplitude within a 200–350 ms window post-stimulus onset,30, 59 whereas the P3 component was defined as the mean amplitude within a 250–500 ms window post-stimulus onset.60

Data analysis