Cardiac coherence and posttraumatic stress disorder in combat veterans.

BACKGROUND: The need for treatment of posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing concern. PTSD has been associated with reduced cardiac coherence (an indicator of heart rate variability [HRV]) and deficits in early stage information processing (attention and immediate memory) in different studies. However, the co-occurrence of reduced coherence and cognition in combat veterans with PTSD has not been studied before. PRIMARY STUDY OBJECTIVE: A pilot study was undertaken to assess the covariance of coherence and information processing in combat veterans. An additional study goal was assessment of effects of HRV biofeedback (HRVB) on coherence and information processing in these veterans. METHODS/DESIGN: A two-group (combat veterans with and without PTSD), pre-post study of coherence and information processing was employed with baseline psychometric covariates. SETTING: The study was conducted at a VA Medical Center outpatient mental health clinic. PARTICIPANTS: Five combat veterans from Iraq or Afghanistan with PTSD and five active-duty soldiers with comparable combat exposure who were without PTSD. INTERVENTION: Participants met with an HRVB professional once weekly for 4 weeks and received visual feedback in HRV patterns while receiving training in resonance frequency breathing and positive emotion induction. PRIMARY OUTCOME MEASURES: Cardiac coherence, word list learning, commissions (false alarms) in go-no go reaction time, digits backward. RESULTS: Cardiac coherence was achieved in all participants, and the increase in coherence ratio was significant post-HRVB training. Significant improvements in the information processing indicators were achieved. Degree of increase in coherence was the likely mediator of cognitive improvement. CONCLUSION: Cardiac coherence is an index of strength of control of parasympathetic cardiac deceleration in an individual that has cardinal importance for the individual's attention and affect regulation.

Conditioning of transcranial magnetic stimulation: evidence of sensory-induced responding and prepulse inhibition.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex. Classical conditioning is a phenomenon of developed associations between stimuli. Our primary objective was to determine whether TMS effects could be conditioned. Prepulse inhibition represents another relationship between two stimuli, and a secondary assessment was performed to explore this relationship. METHODS: An auditory-visual conditioning stimulus (CS) was paired with the TMS unconditioned stimulus (US) over motor cortex producing a motor-evoked potential (MEP) unconditioned response (UR). Two versions of the CS-US pairing paradigms were tested, one with a short intertrial interval (ITI) and another with a long ITI. The short ITI paradigm had more CS-US pairings and shorter session duration than the long ITI paradigm. Tests for conditioned responses (CRs) were performed following CS-US pairing (CS+/US+), by presenting the CS alone (CS+/US-). Reverse testing was also performed after CS-US pairing (CS+/US+) in separate sessions, by presenting the US alone (CS-/US+). RESULTS: Evidence for CRs was found only with the short ITI paradigm. The magnitudes of CRs were smaller than TMS-induced MEPs, and the CRs were found only in a percentage of tests. Prepulse inhibition was robustly evident for the long ITI paradigm, but not for the short ITI paradigm. CONCLUSIONS: We have found evidence that classical conditioning principles can be applied to brain stimulation in humans. These findings provide a method for exploring brain and behavioral relationships in humans, as well as suggesting approaches to enhance therapeutic uses of TMS or other forms of brain stimulation.

Prefrontal control of trace eyeblink conditioning in rabbits (Oryctolagus cuniculus) II: effects of type of unconditioned stimulus (airpuff vs. periorbital shock) and unconditioned stimulus intensity.

Previous research has implicated the medial prefrontal cortex (mPFC) in the control of classically conditioned autonomic and somatomotor responses. In eyeblink (EB) classical conditioning prefrontal involvement appears to be limited to paradigms that are more difficult to learn, in that acquisition is slower. These include trace conditioning and discrimination/reversal. Some of this research suggests that the participation of mPFC in classical EB conditioning is related to the intensity or type of unconditioned stimulus (US) employed. In the present two experiments we thus studied the effects of manipulation of periorbital shock intensity as the US in Experiment 1 and in Experiment 2 the intensity of a corneal airpuff as the US on Pavlovian trace EB conditioning. The results indicate that there are optimal intensities of both airpuff and periorbital shock as the US in the demonstration of mPFC control of trace classical EB conditioning.

Disruption of bradycardia associated with discriminative conditioning in combat veterans with PTSD.

The effects of combat-related posttraumatic stress disorder (PTSD) on heart rate (HR) responding associated with a discriminative delay eyeblink (EB) conditioning paradigm are reported. Combat PTSD+, Combat PTSD-, and Noncombat PTSD- veterans were assessed with psychometric self-report measures, and baseline heart rate variability (HRV) was measured before receiving a 72-trial session of discriminative EB classical conditioning. Two types (red or green light) of conditioned stimuli (CS) were used: one (CS+) predicted a tone, followed immediately by an aversive stimulus (corneal airpuff); the other (CS-) predicted a tone alone, not followed by the airpuff. The light signal was presented for 5 seconds, during which HR was measured. On all psychometric measures, the PTSD+ subgroup was significantly different from the PTSD- subgroups (Combat + Noncombat), and the PTSD- subgroups did not significantly differ from each other. A linear deceleration in HR to CS+ and CS- signals was found in the combined PTSD- subgroup and on CS- trials in the PTSD+ subgroup, but was not present on CS+ trials in the PTSD+ subgroup. Results are interpreted with respect to a behavioral stages model of conditioned bradycardia and in terms of neural substrates which are both critical to HR conditioning and known to be abnormal in PTSD.

Impairments in trace EB conditioning by knife-cut lesions to the fornix in rabbits: reversal by galantamine.

Previous work in our laboratory demonstrated that galantamine, a cholinesterase inhibitor and weak cholinergic agonist, facilitated classical trace eyeblink conditioning in healthy, young rabbits [Simon, B. B., Knuckley, B., & Powell, D. A. (2004). Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learning & Memory, 11(1), 116-122.]. The current study investigated the effects of galantamine (0.0 or 3.0mg/kg) in rabbits sustaining knife-cut lesions to the fimbria-fornix, a major projection pathway connecting the hippocampus to cortical and subcortical brain structures involved in the formation of long-term memories. Two experiments were conducted. Experiment one assessed the effects of knife-cut lesions to the fornix or sham surgeries on trace eyeblink (EB) conditioning. Results indicate that fornix lesions significantly retarded EB conditioning when trace parameters were employed. Experiment 2 assessed whether treatment with galantamine would reverse the deficits caused by fornix damage. Results indicate that 3.0mg/kg GAL reversed trace EB conditioning deficits in animals with fornix knife-cut lesions. These findings suggest that galantamine may provide benefit in the reversal of cognitive dysfunction following certain types of brain damage, especially damage involving hippocampal structures.

Post-training lesions of the medial prefrontal cortex interfere with subsequent performance of trace eyeblink conditioning.

Rabbits were trained on trace eyeblink (EB) conditioning until they reached a criterion of 10 consecutive EB conditioned responses (CRs). Electrolytic lesions were made in the medial prefrontal cortex (mPFC) centered on the prelimbic area (Brodmann's area 32), at five different intervals after training. These included immediately, 24 h, 1 and 2 weeks, and 1 month after training. Separate groups of animals received sham lesions at these same intervals after training. After a 2 week postoperative recovery period, all animals were retested for 3 d on trace conditioning, using the same parameters used during preoperative training. Mean EB conditioning performance deficits occurred in the animals with mPFC lesions compared with sham-lesioned animals on the first day of retesting in all five groups. However, by the second or third day of retesting, the rabbits with lesions were performing at a level that was comparable with that of sham animals. Rabbits that received more posterolateral lesions of the neocortex did not, however, show postoperative conditioning deficits. A comparison of percentage EB CRs of animals with postoperative training with that of animals that received mPFC lesions before training suggests that the mPFC post-training lesions produce damage to a retrieval process and not to a storage site or an acquisition process.

PTSD symptoms, demographic characteristics, and functional status among veterans treated in VA primary care clinics.

We hypothesized that PTSD symptomatology would have an inverse relationship with functional status and would vary as a function of sociodemographic variables. Primary care patients (N = 513) at two VA Medical Centers were randomly selected and recruited to participate. After adjustment for other demographic variables, PTSD symptom levels were significantly related to age (younger patients had more severe symptoms), employment status (disabled persons had higher symptom levels), war zone experience, and clinic location. PTSD symptomatology was inversely related to mental and physical functioning, even after control for potential confounding. These findings have implications for screening and service delivery in VA primary care clinics, and support the more general finding in the literature that PTSD is associated with impaired functioning.

Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits.

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of an eyeblink (EB) classical conditioning task in healthy, young animals. We trained 24 rabbits (n = 8/group) in a 1000-msec trace Pavlovian EB conditioning paradigm in which a tone conditioned stimulus (CS) was presented for 500 msec, followed by a 500-msec trace period in which no stimuli were presented. A 100-msec corneal airpuff was the unconditioned stimulus (US). Acquisition sessions, consisting of 100 trials each, occurred daily for 10 consecutive days, followed by 3 d of extinction training. Animals were treated with one of three doses of GAL (0.0-3.0 mg/kg) prior to each session. Animals that received 3.0 mg/kg GAL showed significantly more EB conditioned responses (CRs) in fewer training trials than animals receiving either 1.5 mg/kg GAL or vehicle injections. GAL had no effect on CR performance during extinction. Pseudoconditioning control experiments, consisting of 200 explicitly unpaired tone-puff presentations indicated that GAL did not increase reactivity to the CS or US. These findings indicate that GAL may improve acquisition of moderately difficult associative learning tasks in healthy young organisms.

Mediodorsal thalamic lesions impair trace eyeblink conditioning in the rabbit.

Rabbits received lesions of the mediodorsal nucleus of the thalamus (MDN) or sham lesions and were subjected to classical eyeblink (EB) and heart rate (HR) conditioning. All animals received trace conditioning, with a.5-sec tone conditioned stimulus, a .5-sec trace period, and a 50-msec periorbital shock unconditioned stimulus. Animals with MDN lesions acquired the EB conditioned response (CR) more slowly than sham-lesioned animals. However, previous studies have shown that MDN damage does not affect delay conditioning using either .5-sec or 1-sec interstimulus intervals. The lesions had no significant effect on the HR CR. These results suggest that information processed by MDN and relayed to the prefrontal cortex is required for somatomotor response selection under nonoptimal learning conditions.